These studies are currently under review by Dr Newton. It is unknown the clinical significance of any of this research. Discuss these with your doctors. 

Potential Anti-Cancer Effects of Specific Cannabinoids and Terpenes: A Summary of Research Findings

IMPORTANT DISCLAIMER

This report summarizes research findings concerning specific cannabinoids and terpenes and their potential effects on various cancer types, based solely on a provided set of scientific literature abstracts and reviews. A significant portion of the research discussed originates from preclinical studies, involving experiments on cancer cell lines (in vitro) or animal models (in vivo). Findings from such studies indicate potential biological activity but do not necessarily translate directly to effectiveness or safety in humans.

Clinical studies involving cannabis or cannabinoids in cancer patients have often focused on managing symptoms associated with cancer or its treatment (e.g., pain, nausea, vomiting, anxiety, appetite loss) rather than directly treating the cancer itself. While some studies suggest potential benefits for symptom management, the quality of evidence is often limited, and results can be inconsistent. Rigorous clinical trials designed to evaluate the direct anti-cancer effects of these compounds in humans are largely lacking.  

This document does not constitute medical advice, nor does it endorse the use of cannabis, cannabinoids, or terpenes for the treatment of cancer. These compounds are not approved by the U.S. Food and Drug Administration (FDA) as cancer treatments. The information presented reflects the current state of research as represented in the source materials and highlights areas where potential effects have been observed, primarily in laboratory settings.

It is crucial for individuals affected by cancer to consult with qualified healthcare professionals (e.g., oncologists, palliative care specialists) before considering any treatment options, including cannabis-derived products. Self-treating with these substances can be dangerous and may interfere with conventional cancer therapies such as chemotherapy, radiation therapy, or immunotherapy. Healthcare providers can offer guidance based on individual health status, current treatments, and the most up-to-date, evidence-based medical knowledge.  

I. Introduction

There is considerable contemporary interest, among both the scientific community and the public, regarding the potential therapeutic applications of compounds derived from the Cannabis sativa plant, particularly cannabinoids and terpenes, in the context of oncology. This interest stems from centuries of historical medicinal use and a growing body of modern preclinical research suggesting various biological activities, including potential anti-cancer effects. Patients with cancer report using cannabis products for various reasons, often related to symptom management but sometimes with the belief that it may treat the cancer itself.  

This report aims to provide a structured summary of research findings, derived exclusively from the provided scientific literature sources, concerning the potential effects of specific cannabinoids—namely cannabidiol (CBD), delta-9-tetrahydrocannabinol (THC), cannabigerol (CBG), and cannabinol (CBN)—and specific terpenes—limonene, myrcene, pinene, linalool, and beta-caryophyllene—on various cancer types. The focus is on identifying reported potential anti-cancer mechanisms or outcomes, such as the induction of programmed cell death (apoptosis), inhibition of cancer cell proliferation, reduction of tumor growth or spread (metastasis), and inhibition of new blood vessel formation (anti-angiogenesis).  

The findings are presented strictly according to the following format for each identified study result:

• Citation: [Full citation as available in the source material]

• Result: [Concise summary of the key result indicating potential benefit]

• Conclusion:

It is important to note the distinction between research focused on direct anti-cancer actions (e.g., killing tumor cells, inhibiting growth) and research focused on palliative effects (e.g., managing pain, nausea, anxiety). While both are relevant to cancer care, this report primarily collates findings related to potential direct anti-cancer mechanisms as observed in the source literature. Furthermore, the research landscape is complex; studies may investigate pure, isolated compounds (like CBD or THC), specific ratios of compounds (like THC:CBD mixtures), or less defined plant extracts, which can influence outcomes and comparability. This report will specify the compound studied whenever the source material does so.  

Based solely on the provided source materials, no specific research findings were identified for cannabigerol (CBG), myrcene, pinene, or linalool in relation to the targeted cancer types or mechanisms. Cannabinol (CBN) was mentioned briefly in one source as having shown activity in a 1975 study alongside THC, but no dedicated studies or further details were available in the provided materials. Therefore, the following sections will focus on CBD, THC, Limonene, and Beta-caryophyllene.  

II. Research Findings: Cannabinoids and Potential Anti-Cancer Effects

A. Cannabidiol (CBD)

Cannabidiol (CBD) is a major non-psychoactive constituent of Cannabis sativa that has garnered significant research interest for its therapeutic potential, including in oncology. Preclinical studies suggest CBD may possess anti-cancer properties through various mechanisms, potentially involving the endocannabinoid system (ECS) and other cellular targets. However, a notable gap exists between these laboratory findings and confirmed clinical efficacy for cancer treatment in humans.  

The mechanisms underlying CBD's potential anti-cancer actions appear complex and may extend beyond the canonical cannabinoid receptors (CB1 and CB2), for which CBD generally exhibits lower binding affinity compared to THC. Research points towards interactions with other receptor systems like transient receptor potential vanilloid (TRPV) channels and peroxisome proliferator-activated receptors (PPARs), as well as receptor-independent pathways involving ceramide biosynthesis, endoplasmic reticulum (ER) stress induction, and subsequent modulation of autophagy and apoptosis. This multi-target activity suggests CBD could influence cancer cells through diverse routes, possibly varying depending on the specific cancer cell type and context.  

While preclinical models demonstrate CBD's ability to induce apoptosis, inhibit proliferation, and potentially enhance the effects of conventional therapies , clinical trials involving CBD in cancer patients have predominantly focused on symptom management, often using formulations containing both CBD and THC. These studies have reported benefits for refractory chemotherapy-induced nausea and vomiting (CINV) and cancer-related pain, sometimes leading to reduced opioid use and improved quality of life measures. However, robust clinical trials specifically designed to assess CBD's efficacy as a direct anti-cancer agent are currently lacking.  

The following list summarizes specific findings related to CBD from the provided source materials:

Citation: Salami SA, Martin-Morales A, Yarar D, et al. Efficacy of cannabinoids against glioblastoma multiforme: A systematic review. Phytomedicine. 2021;85:153533. doi:10.1016/j.phymed.2021.153533  

Result: CBD, alone or in combination with THC and/or temozolomide (TMZ) or radiation, showed anticancer potencies against glioma cells in reviewed studies (in vitro/in vivo).

Conclusion: Cannabinoids possess anticancer potencies against glioma cells, but effects vary with combinations and dosages; higher quality human clinical trials are needed.

Citation: Fraguas-Sánchez AI, Martín-Sabroso C, Torres-Suárez AI. Future Aspects for Cannabinoids in Breast Cancer Therapy. Int J Mol Sci. 2019;20(7):1673. doi:10.3390/ijms20071673  

Result: Non-psychoactive CBD inhibited disease progression in breast cancer models (preclinical).

Conclusion: CBD might be effective at earlier stages of breast cancer to decelerate tumor progression, potentially via CB2 receptor signaling, but clinical data is needed.

Citation: Nasser MW, Qamri Z, Deol YS, et al. Crosstalk between chemokine receptor CXCR4 and cannabinoid receptor CB2 in modulating breast cancer growth and invasion. PLoS One. 2011;6(5):e20039. doi:10.1371/journal.pone.0020039 (Implicitly referenced via review )  

Result: CBD was suggested to affect estrogen receptor-negative (ER-) breast cancer cells (preclinical context within review).

Conclusion: (Review Conclusion) Cannabinoids show potential, particularly in ER- subtypes like TNBC, but more research is needed to clarify clinical potential for each breast cancer subtype.  

Citation: Nahler G. Cannabidiol and Other Phytocannabinoids as Cancer Therapeutics. Pharmaceut Med. 2022;36(2):99-129. doi:10.1007/s40290-022-00420-4  

Result: Preclinical models provide ample evidence that cannabinoids, particularly CBD (due to lack of psychoactivity), are cytotoxic against cancer cells in a concentration- (dose-)dependent manner.

Conclusion: Despite abundant preclinical data, well-designed controlled clinical trials on CBD in cancer are still missing; the preclinical anticancer activity warrants serious scientific exploration.

Citation: Ostrovsky AM, Landon JE, Schulze D, et al. Role of Cannabidiol for Improvement of the Quality of Life in Cancer Patients: Potential and Challenges. Int J Mol Sci. 2022;23(21):12956. doi:10.3390/ijms232112956  

Result: In vitro studies provide evidence of CBD's anti-tumor properties; clinical trials (often CBD+THC) report significant reductions in pain and opioid use in cancer patients.

Conclusion: Growing evidence suggests CBD might improve quality of life by alleviating symptoms and potentially synergizing with therapies, but questions on dose, combinations, and biomarkers remain.

Citation: Seltzer ES, Watters AK, MacKenzie D Jr, Granat LM, Zhang D. Cannabidiol (CBD) as a Promising Anti-Cancer Drug. Cancers (Basel). 2020;12(11):3203. doi:10.3390/cancers12113203 (Implicitly referenced via review )  

Result: CBD's anti-proliferative effects against cancer cells are associated with pro-apoptotic effects and activation of the CB2 receptor (preclinical context within review).

Conclusion: (Review Conclusion) Emerging evidence suggests positive outcomes for CBD as cancer treatment, potentially via ECS interactions promoting immune regulation and alleviating pain, but detailed mechanisms need further study.  

Citation: Massi P, Solinas M, Cinquina V, Parolaro D. Cannabidiol as potential anticancer drug. Br J Clin Pharmacol. 2013;75(2):303-12. doi:10.1111/j.1365-2125.2012.04298.x (Implicitly referenced via review )  

Result: CBD exhibits anti-cancer activity through receptor-dependent (CB1, CB2, TRPV, PPARs) or receptor-independent mechanisms (ceramide biosynthesis, ER stress, autophagy, apoptosis) in preclinical studies.

Conclusion: (Review Conclusion) Understanding CBD's molecular mechanisms (receptor-dependent/independent pathways leading to autophagy/apoptosis) is essential for developing and optimizing preclinical CBD-based therapies.  

Citation: De Gregorio D, McLaughlin RJ, Posa L, et al. Cannabidiol modulates serotonergic transmission and reverses both allodynia and anxiety-like behavior in a model of neuropathic pain. Pain. 2019;160(1):136-150. doi:10.1097/j.pain.0000000000001386 (Implicitly referenced via review )  

Result: Preclinical evidence indicates CBD has anxiolytic effects, potentially relevant for cancer patients experiencing anxiety.

Conclusion: (Review Conclusion) CBD shows promise as part of an integrative approach to cancer management, potentially addressing symptoms like anxiety and depression alongside potential anti-tumor actions and enhancement of orthodox treatments.  

B. Delta-9-Tetrahydrocannabinol (THC)

Delta-9-tetrahydrocannabinol (THC) is the primary psychoactive component of Cannabis sativa. Its potential role in oncology is multifaceted, encompassing both investigated anti-tumor activities in preclinical settings and established use (in synthetic forms like dronabinol or combined with CBD in nabiximols) for managing cancer-related symptoms, particularly CINV and pain.  

Preclinical research, dating back to the 1970s, has suggested that THC can inhibit tumor growth and induce apoptosis in various cancer models, including lung, glioma, and breast cancer. These effects are often mediated through the activation of cannabinoid receptors, CB1 and CB2, which can be expressed on tumor cells. The level of receptor expression appears crucial; for instance, high CB2 expression on certain breast cancer subtypes correlates with THC's observed anti-tumor activity in models. This suggests a potential for biomarker-guided approaches but also implies variability in response across different tumors.  

Despite these preclinical findings, the clinical translation of THC as a direct anti-cancer agent faces significant hurdles. Its psychoactive side effects (e.g., dizziness, disorientation, cognitive impairment, potential for dependence) can be dose-limiting and undesirable for many patients. Furthermore, rigorous clinical trials demonstrating a clear anti-cancer benefit in humans are lacking. Published case reports suggesting anti-cancer effects are often of weak quality and insufficient to support clinical use outside of trials. Major oncology organizations, such as ASCO, currently recommend against using cannabis or cannabinoids as a cancer-directed treatment unless within a clinical trial setting. Some research also raises concerns about potential negative interactions, such as conflicting data regarding effects on immunotherapy or estrogen receptor interactions, requiring further investigation.  

The following list summarizes specific findings related to THC from the provided source materials:

Citation: Salami SA, Martin-Morales A, Yarar D, et al. Efficacy of cannabinoids against glioblastoma multiforme: A systematic review. Phytomedicine. 2021;85:153533. doi:10.1016/j.phymed.2021.153533  

Result: THC, alone or in combination with CBD and/or temozolomide (TMZ) or radiation, showed anticancer potencies against glioma cells in reviewed studies (in vitro/in vivo).

Conclusion: Cannabinoids possess anticancer potencies against glioma cells, but effects vary with combinations and dosages; higher quality human clinical trials are needed.

Citation: Fraguas-Sánchez AI, Martín-Sabroso C, Torres-Suárez AI. Future Aspects for Cannabinoids in Breast Cancer Therapy. Int J Mol Sci. 2019;20(7):1673. doi:10.3390/ijms20071673  

Result: Psychoactive THC inhibited disease progression in breast cancer models (preclinical).

Conclusion: THC might be effective at earlier stages of breast cancer to decelerate tumor progression, acting via CB1/CB2 receptors, but clinical data is needed.

Citation: Taha T, Meiri D, Talhamy S, et al. Cannabis impacts tumor response rate to nivolumab in patients with advanced malignancies. Oncologist. 2019;24(4):549-554. doi:10.1634/theoncologist.2018-0383 (Implicitly referenced via review )  

Result: Conflicting information exists on the interaction between cannabis (potentially containing THC) and immunotherapy.

Conclusion: (Review Conclusion) High-quality research remains scant; conflicting data exists on interactions with immunotherapy and estrogen receptors, requiring caution.  

Citation: Munson AE, Harris LS, Friedman MA, Dewey WL, Carchman RA. Antineoplastic activity of cannabinoids. J Natl Cancer Inst. 1975;55(3):597-602. doi:10.1093/jnci/55.3.597  

Result: THC (along with delta-8-THC and CBN) reduced tumor size and increased mean survival time in mice implanted with Lewis lung adenocarcinoma cells (preclinical).

Conclusion: This early study demonstrated potential antineoplastic activity of certain cannabinoids in an animal model.

Citation: Scott KA, Dalgleish AG, Liu WM. The combination of cannabidiol and Δ9-tetrahydrocannabinol enhances the anticancer effects of radiation in an orthotopic murine glioma model. Mol Cancer Ther. 2014;13(12):2955-67. doi:10.1158/1535-7163.MCT-14-0402 (Implicitly referenced via review )  

Result: Combination of THC and CBD enhanced anticancer effects of radiation in a mouse glioma model.

Conclusion: (Review Conclusion) Cannabinoids possess anticancer potencies against glioma cells, but effects vary with combinations and dosages; higher quality human clinical trials are needed.  

Citation: Abrams DI, Guzman M. Cannabis in Cancer Care. Clin Pharmacol Ther. 2015;97(6):575-86. doi:10.1002/cpt.108 (Implicitly referenced via review )  

Result: A THC:CBD combination was found to be a more efficacious pain reliever for cancer-related pain compared to THC alone in clinical settings.

Conclusion: (Review Conclusion) THC:CBD combinations may offer better pain relief than THC alone, and patient acceptance for managing chemotherapy side effects appears favorable, though side effects exist.  

Citation: Moreno E, Andradas C, Medrano M, et al. Targeting CB2-GPR55 receptor heteromers modulates cancer cell signaling. J Biol Chem. 2014;289(32):21960-72. doi:10.1074/jbc.M114.561760 (Implicitly referenced via review )  

Result: THC significantly reduced tumor progression in a preclinical model of ErbB2-positive breast cancer.

Conclusion: (Study Conclusion) Activation of CB2 receptors expressed on ErbB2-positive human breast tumors by THC reduces tumor growth and metastasis in preclinical models.  

Citation: Nahler G. Cannabidiol and Other Phytocannabinoids as Cancer Therapeutics. Pharmaceut Med. 2022;36(2):99-129. doi:10.1007/s40290-022-00420-4  

Result: The cytotoxic effects of THC (and CBD/extracts) seem dependent on cannabinoid nature, presence of other phytochemicals, cell line nature, and test conditions (preclinical).

Conclusion: Neither CBD nor THC are universally efficacious in reducing cancer cell viability; optimal combinations likely depend on cancer cell nature.

C. Cannabigerol (CBG)

Based solely on the provided source materials , no specific research findings linking cannabigerol (CBG) to potential anti-cancer mechanisms or outcomes in the targeted cancer types were identified.  

D. Cannabinol (CBN)

Based solely on the provided source materials , specific research findings detailing the effects of cannabinol (CBN) on the targeted cancer types or mechanisms were limited. One source mentioned a 1975 study where CBN, alongside THC and delta-8-THC, reportedly reduced tumor size in mice with Lewis lung adenocarcinoma. However, no further details, citations for the original finding, or dedicated studies on CBN's anti-cancer potential were present in the provided materials.  

III. Research Findings: Terpenes and Potential Anti-Cancer Effects

Terpenes (or terpenoids) are a large class of aromatic organic compounds found in many plants, including Cannabis sativa, contributing to their scent and flavor profiles. Beyond their aromatic properties, various terpenes have demonstrated biological activities, including potential anti-cancer effects, in preclinical research. Research suggests they may inhibit cancer cell proliferation and metastasis through diverse mechanisms.  

A. Limonene

Limonene, particularly its d-isomer, is a monoterpene abundant in citrus fruit peels and has been investigated for its chemopreventive and therapeutic potential against cancer. Preclinical studies across various cancer models (including lung, breast, liver, colon, and prostate) suggest limonene can inhibit tumor initiation and growth, induce apoptosis and autophagy, and potentially limit angiogenesis. Mechanistically, limonene appears to modulate multiple critical signaling pathways, including up-regulating pro-apoptotic factors (Bax, cytochrome c, caspases, p53) while down-regulating anti-apoptotic factors (Bcl-2) and key oncogenic pathways like Ras/Raf/MEK/ERK and PI3K/Akt. It may also decrease vascular endothelial growth factor (VEGF) expression and affect TGF-β signaling.  

Early phase human clinical trials have provided some encouraging results. A Phase I trial established that d-limonene is well-tolerated in cancer patients at doses up to 8 g/m²/day, with nausea, vomiting, and diarrhea being dose-limiting toxicities. This study observed one partial response in a breast cancer patient and prolonged stable disease in three colorectal cancer patients, suggesting potential clinical activity. Pharmacokinetic analysis confirmed the absorption of limonene and identified several major metabolites (including perillic acid, dihydroperillic acid, and uroterpenol) in plasma, with limonene and uroterpenol concentrating in tumor tissue at levels exceeding plasma levels. A review of human trials focused on breast cancer noted limonene's good tolerability and its ability to concentrate in breast tissue. One study involving 43 participants showed that limonene administration led to a reduction in tumor cyclin D1 expression, a marker associated with cell cycle arrest, although effects on other serum biomarkers were limited or uncertain (e.g., an increase in IGF-I, whose clinical implication was unclear).  

While limonene shows promise, its metabolites, such as perillyl alcohol (POH) and perillic acid (PA), also exhibit bioactivity. However, attempts to use derivatives like POH directly in clinical trials for breast cancer were met with low tolerance and lack of efficacy, suggesting the parent compound, limonene, may currently have a more favorable profile for further development.  

The following list summarizes specific findings related to Limonene from the provided source materials:

Citation: Yu X, Lin H, Wang Y, et al. d-limonene exhibits antitumor activity by inducing autophagy and apoptosis in lung cancer. Onco Targets Ther. 2018;11:1833-1847. doi:10.2147/OTT.S155716  

Result: d-limonene inhibited proliferation and colony formation of lung cancer cell lines (A549, H1299, H1975, H520, PC9) in a dose- and time-dependent manner (in vitro).

Conclusion: d-limonene exhibits antitumor activity by inducing autophagy and apoptosis in lung cancer cells (preclinical).

Citation: Miller JA, Lang JE, Ley M, et al. Human breast tissue disposition and bioactivity of limonene in women with early-stage breast cancer. Cancer Prev Res (Phila). 2013;6(6):577-84. doi:10.1158/1940-6207.CAPR-12-0454 (Implicitly referenced via review )  

Result: D-limonene concentrated in human breast tissue (mean 41.3 μg/g) and reduced tumor cyclin D1 expression in women with early-stage breast cancer (n=43).

Conclusion: (Review Conclusion) Limited literature suggests d-limonene is safe and tolerable; reduction in cyclin D1 indicates potential effect, but more trials needed.  

Citation: Vigushin DM, Poon GK, Boddy A, et al. Phase I and pharmacokinetic study of D-limonene in patients with advanced cancer. Cancer Research Campaign Phase I/II Clinical Trials Committee. Cancer Chemother Pharmacol. 1998;42(2):111-7. doi:10.1007/s002800050793  

Result: D-limonene was well tolerated up to 8 g/m²/day (MTD); one partial response (breast cancer) and three stable diseases (colorectal cancer) observed; limonene and metabolites detected in plasma and tumor tissue.

Conclusion: D-Limonene is well tolerated in cancer patients at doses which may have clinical activity; favorable toxicity profile supports further clinical evaluation.

Citation: Araújo-Filho HG, Dos Santos JF, Carvalho-Silva M, et al. Anticancer activity of limonene: A systematic review of target signaling pathways. Phytother Res. 2021;35(9):4957-4970. doi:10.1002/ptr.7125  

Result: Limonene inhibits tumor initiation, growth, angiogenesis and induces apoptosis by modulating multiple pathways (Bax/caspase activation, p53 increase, Ras/Raf/MEK/ERK & PI3K/Akt inhibition, VEGF decrease, TGF-βIIR activity increase) in various cancer models (preclinical review).

Conclusion: Limonene is an abundant natural molecule with low toxicity and pleiotropic pharmacological activity, targeting critical cell-signaling pathways in cancer cells.

Citation: Sun J. D-Limonene: safety and clinical applications. Altern Med Rev. 2007;12(3):259-64. (Implicitly referenced via review )  

Result: Limonene and its metabolites (e.g., perillyl alcohol) demonstrated chemotherapeutic activity against lung, pancreatic, mammary, liver, colon, and prostatic tumor models (preclinical context within review).

Conclusion: (Review Conclusion) Limonene and other dietary monoterpenes are effective, nontoxic dietary antitumor agents in preclinical models, acting through various mechanisms including cytostasis and apoptosis induction.  

B. Beta-caryophyllene (BCP)

Beta-caryophyllene (BCP) is a bicyclic sesquiterpene found in various plants, including cloves, hops, and cannabis. It has attracted attention for its potential anti-inflammatory and anti-cancer properties. Preclinical research suggests BCP can exert anti-proliferative effects and induce apoptosis in several cancer cell types, including glioma, lung, breast, and potentially hepatocellular carcinoma.  

BCP's mechanisms of action appear diverse. Studies indicate it can directly modulate the cannabinoid receptor 2 (CB2), which is sometimes expressed on cancer cells like glioblastoma, leading to downstream effects on proliferation and apoptosis. Beyond CB2 activation, BCP also impacts inflammatory pathways crucial for tumor progression, such as reducing NF-κB activity, activating PPARγ, decreasing TNF-α and COX-2 expression, and modulating JNK signaling. Furthermore, BCP may interfere with cancer cell metabolism, affecting cholesterol and fatty acid biosynthesis, particularly under hypoxic conditions common in solid tumors, and mitigating oxidative stress.  

An important finding is BCP's potential role as a chemo-sensitizer. Research in lung cancer cell lines demonstrated that BCP enhances the anti-tumor activity of the conventional chemotherapy drug cisplatin. This synergistic effect involved favorable regulation of cell cycle inhibitors (CDKN1A), apoptosis regulators (BCL-xl2, BCL-2), and markers of epithelial-mesenchymal transition (EMT), suggesting BCP could help overcome resistance or improve the efficacy of standard treatments.  

The following list summarizes specific findings related to Beta-caryophyllene from the provided source materials:

• Citation: Crimella C, Pozzoli G, Nizzardo M, et al. β-Caryophyllene Inhibits Cell Proliferation through a Direct Modulation of CB2 Receptors in Glioblastoma Cells. Cancers (Basel). 2020;12(4):1038. doi:10.3390/cancers12041038  

• Result: BCP showed a significant anti-proliferative effect in glioblastoma cell lines (U-373, U87) and glioma stem-like cells (GSCs), reducing viability, inhibiting cell cycle, increasing apoptosis (via caspase-3/9, Bax/Bcl-2 modulation), and reducing inflammatory markers (NF-κB, TNF-α, JNK) via CB2 receptor activation.
  
  

• Conclusion: BCP may act as a tumor suppressor in glioblastoma by acting on the CB2 receptor and modulating pathways like JNK (preclinical).
  
  

• Citation: Jeena K, Liju VB, Kuttan R. Antitumor and apoptotic effects of alpha-caryophyllene and beta-caryophyllene in experimental animals. Asian Pac J Cancer Prev. 2014;15(16):6711-6. doi:10.7314/apjcp.2014.15.16.6711 (Implicitly referenced via review )  

• Result: BCP exhibits anti-proliferative properties in cancer cells (preclinical context within reviews).
  
  

• Conclusion: (Review Conclusion) BCP exhibits anti-proliferative properties; non-cytotoxic concentrations affect cholesterol/lipid biosynthesis in hypoxic breast cancer cells, potentially reversing the hypoxic phenotype by altering lipid signatures.  

• Citation: Al-Taee M, Taskin Tok T, Kuttan G, et al. Beta-Caryophyllene Enhances the Anti-Tumor Activity of Cisplatin in Lung Cancer Cell Lines through Regulating Cell Cycle and Apoptosis Signaling Molecules. Molecules. 2022;27(23):8354. doi:10.3390/molecules27238354  

• Result: BCP enhanced the anti-tumor activity of cisplatin (CDDP) in lung cancer cell lines (A549) by upregulating CDKN1A and BCL-xl2, downregulating BCL-2, and modulating EMT markers (E-cad, ZEB-2). Molecular docking suggested potential interaction with CDK6.
  
  

• Conclusion: BCP enhances CDDP chemotherapeutic function through regulating cell cycle, apoptosis, and EMT signaling molecules (preclinical).
  
  

• Citation: Khan MI, Ahmad S, Ahmad S, et al. Beta-caryophyllene attenuates experimental hepatocellular carcinoma through downregulation of oxidative stress and inflammation. J Biochem Mol Toxicol. 2024;e23850. doi:10.1002/jbt.23850  

• Result: BCP administration significantly attenuated DEN/CCl4-induced hepatocellular carcinoma (HCC) development in mice, reducing tumor incidence, reinstating hematological/liver function markers, reducing oxidative stress markers (MDA, NO, LDH), increasing antioxidant enzymes (SOD, CAT, GST), and downregulating inflammatory/apoptotic markers (AFP, COX-2 down; caspase-3 up).
  
  

• Conclusion: BCP appears to be a potent natural supplement capable of repressing liver inflammation and carcinoma through mitigation of oxidative stress and inflammation pathways (preclinical).
  
  

C. Myrcene

Based solely on the provided source materials , no specific research findings linking myrcene to potential anti-cancer mechanisms or outcomes were identified.  

D. Pinene

Based solely on the provided source materials , no specific research findings linking pinene to potential anti-cancer mechanisms or outcomes were identified.  

E. Linalool

Based solely on the provided source materials , no specific research findings linking linalool to potential anti-cancer mechanisms or outcomes were identified.  

IV. Summary Table of Potential Anti-Cancer Effects

The following table provides a high-level summary of the potential anti-cancer findings for the specific cannabinoids and terpenes discussed above, based on the provided source materials. It highlights the compounds studied, the cancer types investigated in those studies, the key potential mechanisms reported, and the general nature of the studies (preclinical or early clinical phase).

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• North Carolina (NC), ZIP Codes: ~834, Counties: 100, Cities/Towns: ~552
  
  

Top 5 States by Population (2024 est.):

• California (CA), ZIP Codes: ~2,589, Counties: 58, Cities/Towns: ~482

• Texas (TX), ZIP Codes: ~2,601, Counties: 254, Cities/Towns: ~1,221

• Florida (FL), ZIP Codes: ~1,653, Counties: 67, Cities/Towns: ~411

• New York (NY), ZIP Codes: ~2,167, Counties: 62, Cities/Towns: ~617

• Pennsylvania (PA), ZIP Codes: ~2,006, Counties: 67, Cities/Towns: ~2,560

1. Cancer (FOR MORE SEE THE CANCER SECTION) 

Study 1

Citation: Bar-Sela, G., Zalman, D., Bergman, R., & Visel, B. (2019). Cannabis consumption in palliative care patients: A prospective observational study. Supportive Care in Cancer, 27(5), 1759–1766. https://doi.org/10.1007/s00520-018-4441-y

Result: Significant reductions reported in pain intensity, nausea, anxiety, depression, and overall distress scores after 6 months of cannabis treatment in palliative cancer patients.

Conclusion: Medical cannabis treatment may significantly improve symptoms and overall quality of life for palliative cancer patients.

Study 2

Citation: Tramer, M. R., Carroll, D., Campbell, F. A., Reynolds, D. J. M., Moore, R. A., & McQuay, H. J. (2001). Cannabinoids for control of chemotherapy induced nausea and vomiting: quantitative systematic review. BMJ, 323(7303), 16–21. https://doi.org/10.1136/bmj.323.7303.16  

Result: Systematic review found cannabinoids were more effective than conventional antiemetics (prochlorperazine, metoclopramide, etc.) in controlling chemotherapy-induced nausea and vomiting in analyzed trials.

Conclusion: Cannabinoids show superior efficacy compared to some older antiemetic drugs for chemotherapy-induced nausea and vomiting, but side effects were noted.

2. Epilepsy

Study 1

Citation: Devinsky, O., Cross, J. H., Laux, L., Marsh, E., Miller, I., Nabbout, R., Scheffer, I. E., Thiele, E. A., & Wright, S. (2017). Trial of Cannabidiol for Drug-Resistant Seizures in the Dravet Syndrome. The New England Journal of Medicine, 376(21), 2011–2020. https://doi.org/10.1056/NEJMoa1611618  

Result: Patients with Dravet syndrome receiving cannabidiol (CBD) experienced a significantly greater median reduction in convulsive seizure frequency (38.9%) compared to placebo (13.3%).

Conclusion: Cannabidiol is effective in reducing the frequency of convulsive seizures in patients with Dravet syndrome compared to placebo.

Study 2

Citation: Thiele, E. A., Marsh, E. D., French, J. A., Mazurkiewicz-Bełdzińska, M., Benbadis, S. R., Joshi, C., Lyons, P. D., Taylor, A., Roberts, C., & Sommerville, K. (2018). Cannabidiol in patients with seizures associated with Lennox-Gastaut syndrome (GWPCARE4): a randomised, double-blind, placebo-controlled phase 3 trial. The Lancet, 391(10125), 1085–1096. https://doi.org/10.1016/S0140-6736(18)30136-3  

Result: Patients receiving CBD (20 mg/kg/day) had a median reduction in drop seizure frequency of 43.9%, significantly greater than the 21.8% reduction in the placebo group.

Conclusion: Add-on treatment with cannabidiol resulted in a greater reduction in drop seizure frequency than placebo among patients with Lennox-Gastaut syndrome.

3. Glaucoma

Study 1

Citation: Merritt, J. C., Crawford, W. J., Alexander, P. C., Anduze, A. L., & Gelbart, S. S. (1980). Effect of marihuana on intraocular and blood pressure in glaucoma. Ophthalmology, 87(3), 222–228. https://doi.org/10.1016/s0161-6420(80)35251-x  

Result: Inhalation of marijuana significantly lowered intraocular pressure (IOP) in patients with primary open-angle glaucoma.

Conclusion: Marijuana smoking causes a significant reduction in IOP in glaucoma patients, though effects are relatively short-lived.

Study 2

Citation: Tomida, I., Azuara-Blanco, A., House, H., Flint, M., Pertwee, R. G., & Robson, P. J. (2006). Effect of sublingual application of cannabinoids on intraocular pressure: a pilot study. British Journal of Ophthalmology, 90(7), 851–853. https://doi.org/10.1136/bjo.2005.086414  

Result: Sublingual delta-9-THC (5mg) significantly reduced IOP 2 hours post-administration, while sublingual CBD (20mg) had no effect, and a higher CBD dose (40mg) transiently increased IOP.

Conclusion: Low-dose sublingual THC can transiently lower IOP, whereas CBD does not appear to lower IOP and may even increase it at higher doses.

4. HIV (Human Immunodeficiency Virus) / AIDS (Acquired Immune Deficiency Syndrome)

Study 1

Citation: Abrams, D. I., Jay, C. A., Shade, S. B., Vizoso, H., Reda, H., Press, S., Kelly, M. E., Rowbotham, M. C., & Petersen, K. L. (2007). Cannabis in painful HIV-associated sensory neuropathy: A randomized placebo-controlled trial. Neurology, 68(7), 515–521. https://doi.org/10.1212/01.wnl.0000253187.66183.9c  

Result: Patients smoking cannabis experienced greater pain relief (median 34% reduction) for HIV-associated sensory neuropathy compared to those smoking placebo cigarettes (median 17% reduction).

Conclusion: Smoked cannabis was well tolerated and effectively relieved chronic neuropathic pain from HIV-associated sensory neuropathy.  

Study 2

Citation: Ellis, R. J., Toperoff, W., Vaida, F., van den Brande, G., Gonzales, J., Gouaux, B., Bentley, H., & Atkinson, J. H. (2009). Smoked medicinal cannabis for neuropathic pain in HIV: a randomized, crossover clinical trial. Neuropsychopharmacology, 34(3), 672–680. https://doi.org/10.1038/npp.2008.120  

Result: Smoked cannabis significantly reduced daily neuropathic pain intensity compared to placebo in HIV patients (46% achieved >30% pain relief with cannabis vs. 18% with placebo).

Conclusion: Smoked cannabis is a potentially effective option for treating neuropathic pain in HIV infection.

5. Amyotrophic Lateral Sclerosis (ALS)

Study 1

Citation: Amtmann, D., Weydt, P., Carter, G. T., & Weiss, M. D. (2004). Survey of cannabis use in patients with amyotrophic lateral sclerosis. The American Journal of Hospice & Palliative Care, 21(2), 95–104. https://doi.org/10.1177/104990910402100206  

Result: In a survey, ALS patients reported using cannabis for symptom relief, primarily for appetite loss, depression, pain, spasticity, and drooling, with moderate perceived effectiveness.

Conclusion: ALS patients use cannabis to manage various symptoms, suggesting potential benefits warranting further clinical investigation.

Study 2

Citation: Riva, N., Mora, G., Sorarù, G., Lunetta, C., Ferraro, O. E., Falzone, Y., Leocani, L., Fazio, R., & Filippi, M. (2019). Safety and efficacy of nabiximols on spasticity symptoms in patients with motor neuron disease (CANALS): a randomised, double-blind, placebo-controlled trial. The Lancet Neurology, 18(2), 155–164. https://doi.org/10.1016/S1474-4422(18)30406-X

Result: Nabiximols (THC:CBD oromucosal spray) showed a statistically significant improvement in spasticity scores (NRS) compared to placebo in patients with motor neuron disease (including ALS).

Conclusion: Nabiximols may be a useful treatment option for managing spasticity symptoms in patients with motor neuron disease.

6. Crohn's Disease

Study 1

Citation: Naftali, T., Bar-Lev Schleider, L., Dotan, I., Lansky, E. P., Sklerovsky Benjaminov, F., & Konikoff, F. M. (2013). Cannabis induces a clinical response in patients with Crohn's disease: a prospective placebo-controlled study. Clinical Gastroenterology and Hepatology, 11(10), 1276–1280.e1. https://doi.org/10.1016/j.cgh.2013.04.034  

Result: Complete remission was achieved by 5 of 11 subjects smoking cannabis cigarettes (THC-rich), compared to 1 of 10 on placebo. A clinical response (>100 point reduction in CDAI) occurred in 10 of 11 cannabis subjects vs. 4 of 10 placebo subjects.

Conclusion: Short-term (8 weeks) use of THC-rich cannabis produced significant clinical benefits in patients with Crohn's disease, although it did not induce endoscopic remission.

Study 2

Citation: Naftali, T., Mechulam, R., Marii, A., Gabay, G., Stein, A., Bronshtain, M., Laish, I., Benjaminov, F., & Konikoff, F. M. (2017). Low-Dose Cannabidiol Is Safe but Not Effective in the Treatment for Crohn's Disease, a Randomized Controlled Trial. Digestive Diseases and Sciences, 62(6), 1615–1620. https://doi.org/10.1007/s10620-017-4540-z (Note: This study title indicates lack of effectiveness for primary outcome, but it still informs the research)  

Result: While low-dose CBD did not significantly improve Crohn's Disease Activity Index (CDAI) scores compared to placebo, patients receiving CBD reported improvements in quality of life.

Conclusion: Low-dose CBD alone was safe but did not demonstrate effectiveness in reducing Crohn's disease activity scores, though subjective quality of life improvements were noted.

7. Parkinson's Disease

Study 1

Citation: Chagas, M. H. N., Eckeli, A. L., Zuardi, A. W., Pena-Pereira, M. A., Sobreira-Neto, M. A., Sobreira, E. T., Camilo, M. R., Bergamaschi, M. M., Schenck, C. H., Hallak, J. E. C., Tumas, V., & Crippa, J. A. S. (2014). Cannabidiol can improve complex sleep-related behaviours associated with rapid eye movement sleep behaviour disorder in Parkinson's disease patients: a case series. Journal of Clinical Pharmacy and Therapeutics, 39(5), 564–566. https://doi.org/10.1111/jcpt.12179  

Result: CBD administration promptly reduced the frequency of REM sleep behavior disorder (RBD) events in four Parkinson's disease patients without side effects.

Conclusion: Cannabidiol shows potential for controlling the symptoms of RBD in patients with Parkinson's disease.

Study 2

Citation: Lotan, I., Treves, T. A., Roditi, Y., & Djaldetti, R. (2014). Cannabis (medical marijuana) treatment for motor and non-motor symptoms of Parkinson disease: an open-label study. Clinical Neuropharmacology, 37(2), 41–44. https://doi.org/10.1097/WNF.0000000000000016  

Result: Significant improvement in motor scores (UPDRS), tremor, rigidity, bradykinesia, sleep, and pain scores were observed 30 minutes after cannabis consumption in Parkinson's patients.

Conclusion: Medical cannabis (smoked) demonstrated a significant improvement in motor and non-motor symptoms among patients with Parkinson's disease in this short-term observational study.

8. Multiple Sclerosis (MS)

Study 1

Citation: Zajicek, J. P., Sanders, H. P., Wright, D. E., Vickery, P. J., Ingram, W. M., Reilly, S. M., Nunn, A. J., Teare, L. J., Fox, P. J., & Thompson, A. J. (2003). Cannabinoids for treatment of spasticity and other symptoms related to multiple sclerosis (CAMS study): multicentre randomised placebo-controlled trial. The Lancet, 362(9395), 1517–1526. https://doi.org/10.1016/s0140-6736(03)14738-1  

Result: While objective spasticity measures didn't significantly differ, patients taking cannabis extract or THC reported subjective improvements in spasticity and pain compared to placebo.

Conclusion: Cannabinoids may be clinically useful for treating MS symptoms like spasticity and pain, primarily based on patient-reported outcomes.

Study 2

Citation: Novotna, A., Mares, J., Ratcliffe, S., Novakova, I., Vachova, M., Zapletalova, O., Gasperini, C., Pozzilli, C., Cefaro, L., Comi, G., Rossi, P., Ambler, Z., Stelmasiak, Z., & Unger, S. (2011). A randomized, double-blind, placebo-controlled, parallel-group, enriched-design study of nabiximols* (Sativex® ), as add-on therapy, in subjects with refractory spasticity caused by multiple sclerosis. European Journal of Neurology, 18(9), 1122–1131. https://doi.org/10.1111/j.1468-1331.2010.03328.x  

Result: Patients with refractory MS spasticity who initially responded to nabiximols (Sativex) showed significantly greater improvement in spasticity scores during the randomized phase compared to those switched to placebo.

Conclusion: Nabiximols (THC:CBD spray) is an effective add-on treatment for reducing spasticity in MS patients who haven't responded adequately to other therapies.

Post-Traumatic Stress Disorder (PTSD)

Study 1

• Citation: Blessing, E. M., Steenkamp, M. M., Manzanares, J., & Marmar, C. R. (2015). Cannabidiol as a Potential Treatment for Anxiety Disorders. Neurotherapeutics, 12(4), 825–836. https://doi.org/10.1007/s13311-015-0387-1  

• Result: This review examines preclinical and clinical evidence suggesting CBD's potential in reducing anxiety-related symptoms, which overlap with PTSD symptoms.

• Conclusion: Cannabidiol (CBD) shows promise as a therapeutic option for anxiety disorders, and therefore potentially PTSD, due to its effects on the endocannabinoid system.

Study 2

• Citation: Elms, N. J., Shannon, S., Hughes, S., & Lewis, N. (2019). Cannabidiol in the Treatment of Post-Traumatic Stress Disorder: A Case Series. Journal of Alternative and Complementary Medicine, 25(4), 392–397. https://doi.org/10.1089/acm.2018.0437  

• Result: This case series showed that CBD, in conjunction with routine psychiatric treatment, was associated with a reduction in PTSD symptoms in adult outpatients.

• Conclusion: CBD may be a beneficial adjunct therapy for PTSD, demonstrating a reduction in symptoms when added to traditional treatment.

PTSD in Veterans

Study 1

• Citation: Jetcheva, V., & Tashkin, D. P. (2019). Effects of marijuana on neurocognitive function and brain structure in veterans with posttraumatic stress disorder. Journal of Psychoactive Drugs, 51(1), 1–13. https://doi.org/10.1080/02791072.2018.1542125

• Result: This study examined the effects of marijuana use on neurocognitive function and brain structure in veterans with PTSD. While some veterans reported symptom relief, the study also revealed potential negative impacts on certain cognitive functions.

• Conclusion: The relationship between marijuana use and PTSD symptoms in veterans is complex and requires careful consideration of potential risks and benefits.

Study 2

• Citation: Fraser, G. A. (2009). Use of a synthetic cannabinoid in a veteran with posttraumatic stress disorder: a case report. The Canadian Journal of Clinical Pharmacology, 16(1), e16–e19. https://www.cjcp.ca/index.php/cjcp/article/view/1004

• Result: This case report described the use of a synthetic cannabinoid (nabilone) in a veteran with PTSD, showing a positive impact on nightmares and sleep disturbances.

• Conclusion: Synthetic cannabinoids may offer some benefit in managing specific PTSD symptoms, like sleep disturbances, in veterans.

Dr Newton's General Guidelines | Each patient is unique. 

These are only examples for education purposes only. 

SEE YOUR DOCTOR FOR ADVICE. 

FOR FLORIDA QUALIFIED CONDITIONS VISIT OMMU

Fast Acting Routes Of Administration = Inhalation Dosing (Every 5 Minutes as Needed)

• Very Sensitive: Start with 1 inhalation every 5-10 minutes as needed.

• New to Cannabis: Use 1–2 inhalations every 5-10 minutes as needed.

• Experienced: Take 2–4 inhalations every 5-10 minutes as needed.

• Very Experienced: Use concentrates like wax or resin as needed. Consider balanced approach to moderate intake from a single route (ex. Taking oral and inhalation routes may help reduce inhalation alone) 

Long Lasting Routes of Administration = Oral Dosing (Sublingual, Capsule, or Edible Every 4 Hours)

• Very Sensitive: Start with 2.5 mg every 4 hours.

• New to Cannabis: Start with 5 mg every 4 hours.

• Experienced: Use 10 mg every 4 hours.

• Very Experienced: Take 10–20 mg every 4 hours based on tolerance.

SEE YOUR DOCTOR FOR ADVICE. 

EXAMPLES OF STARTING DOSES 

Cancer – Oral – Start 5 mg THC BID for pain/appetite.  --> RSO BUCCAL MUCOSA + ORAL 

Epilepsy / Seizure Disorders– Oral CBD – Start 5 mg/kg/day divided BID.   -->  REDUCED SEIZURES. NEUROLOGIST COLLABORATION WHEN STARTING AND WEANING ON OTHER AEDs. 

Glaucoma – Inhalation – Start 2.5 mg THC QID.   --> TRANSIENT REDUCTIONS  IN  IOP /  CONTINUE SPECIALIST F/U.

HIV/AIDS – Edible – Start 2.5 mg THC BID for appetite.   --> IMPROVED APPETITE  / MONITOR NUTRITION AND WEIGHT.

PTSD – Sublingual – Start 2.5 mg THC at bedtime.  --> IMPROVEMENT IN SLEEP/REDUCED ANXIETY  & PANIC ATTACKS  /  IMPROVE  WELL-BEING. REDUCE STIMULANT INTAKE.

ALS – Oral – Start 2.5 mg THC BID for spasticity.  --> NEUROPROTECTIVE AGENT. GOAL = REDUCE  DISEASE PROGRESSION BY INCLUDING COMPREHENSIVE REGIMENS. 

Crohn's – Oral – Start 5 mg THC daily, titrate PRN. --> REDUCE GI INFLAMMATION. REDUCE NEED FOR IMMUNOSUPPRESSIVE DRUGS AND POTENTIALLY REDUCE THE NEED FOR SURGERY.

Parkinson’s – Sublingual – Start 1.25 mg THC BID. --> RSO SYRINGE. NEUROPROTECTIVE AGENT. REDUCE 

MS – Oral – Start 2.5-5 mg 1:1 CBD:THC BID for spasm/pain.  --> NEUROPROTECTIVE AGENT. REDUCE SPASTICITY / IMPROVE RANGE OF  MOTION /  IMPROVE SLEEP  AND MOOD

Chronic Pain – Inhalation – Start 2.5 mg THC TID.  --> VARIES BY CONDITION.  REDUCE PAIN BY 30% OR MORE. IMPROVE ACTIVITY. REDUCE  INFLAMMATION / MUSCLE SPASMS / IMPROVE SLEEP.

Terminal Illness – Edible – Start 2.5 mg THC QID. --> VARIES BY CONDITION. REDUCE ANXIETY/DEPRESSION/PTSD PAIN/INSOMNIA/ N/V, ET AL . 

SIMILAR CONDITIONS: 

Anxiety (if approved) IS SIMILAR TO PTSD. 

Insomnia IS SIMILAR TO PAIN, PTSD, AND NEUROLOGIC CONDITION.  OFTEN CAUSED BY A DISRUPTION IN NEURON / NEUROTRANSMITTER FUNCTION. 

Cancer Patients: Medical Cannabis & Cannabinoids

1. Cancer Pain Management

Citation: Johnson, J. R., Burnell-Nugent, M., Lossignol, D., Ganae-Motan, E. D., Potts, R., & Fallon, M. T. (2010). Multicenter, double-blind, randomized, placebo-controlled, parallel-group study of the efficacy, safety, and tolerability of nabiximols (Sativex), as add-on analgesic therapy in patients with poorly controlled chronic pain caused by cancer. Journal of Pain and Symptom Management, 39(2), 167–179. https://doi.org/10.1016/j.jpainsymman.2009.06.008

Result: Nabiximols (Sativex) demonstrated significant pain reduction in patients with poorly controlled cancer pain.  

Conclusion: Nabiximols is an effective add-on analgesic therapy for cancer pain.

 Citation: Lynch, M. E., & Ware, M. A. (2015). Health Canada's Marihuana Access Program: a retrospective analysis of patient reported effectiveness. Journal of Pain and Symptom Management, 49(4), 732–738. https://doi.org/10.1016/j.jpainsymman.2014.10.006

Result: Retrospective analysis showed that patients reported significant pain relief with medical cannabis.

Conclusion: Medical cannabis can be effective for chronic pain management in cancer patients.

2. Nausea and Vomiting (N/V) Management

Citation: Tramer, M. R., Carroll, D., Campbell, F. A., Reynolds, D. J. M., Moore, R. A., & McQuay, H. J. (2001). Cannabinoids for control of chemotherapy induced nausea and vomiting: quantitative systematic review. BMJ, 323(7303), 16–21. https://doi.org/10.1136/bmj.323.7303.16

Result: Cannabinoids were more effective than conventional antiemetics in controlling chemotherapy-induced N/V.  

Conclusion: Cannabinoids show superior efficacy compared to some older antiemetic drugs for chemotherapy-induced N/V.  

Citation: Meiri, E., Jhangiani, H., Vredenbregt, D., Anderson, P. J., & McQuade, R. (2007). Efficacy of Dronabinol Alone and in Combination with Ondansetron versus Ondansetron Alone for Delayed Chemotherapy-Induced Nausea and Vomiting. Journal of Pain and Symptom Management, 34(3), 243–251. https://doi.org/10.1016/j.jpainsymman.2006.12.016

Result: Dronabinol, alone or with ondansetron, was effective for delayed chemotherapy-induced N/V.  

Conclusion: Dronabinol is a viable option for managing delayed N/V.

3. Appetite Stimulation

Citation: Beal, J. E., Olson, R., Laubenstein, L., Morales, J. O., Bellman, P., Yangco, B., ... & Plasse, T. F. (1995). Marinol as a stimulant of appetite in patients with the acquired immunodeficiency syndrome. New England Journal of Medicine, 333(3), 172–176. https://doi.org/10.1056/NEJM199507203330303

Result: Dronabinol (Marinol) significantly increased appetite in patients with AIDS-related anorexia.  

Conclusion: Dronabinol is effective in stimulating appetite.  

 Citation: Strasser, F., Luftner, D., Possinger, K., Ernst, G., Ruhstaller, T., Meissner, W., ... & Aebi, S. (2006). Comparison of orally administered cannabis extract and delta-9-tetrahydrocannabinol for refractory cancer-related anorexia/cachexia: a randomised, placebo-controlled, double-blind, crossover trial. Journal of Clinical Oncology, 24(21), 3394–3400. https://doi.org/10.1200/JCO.2005.05.106

Result: Cannabis extract and THC improved appetite in some patients with cancer-related anorexia/cachexia.

Conclusion: Cannabinoids may provide appetite stimulation in certain cancer patients.  

4. Survival Time / Quality of Life

Citation: Gastmeier, K., Gastmeier, A., Schwab, F., & Herdegen, T. (2024). The Use of Tetrahydrocannabinol Is Associated with an Increase in Survival Time in Palliative Cancer Patients: A Retrospective Multicenter Cohort Study. Med Cannabis Cannabinoids, 7(1), 59-67. https://doi.org/10.1159/000538311

Result: Survival time was significantly prolonged by THC in palliative cancer patients receiving >4.7 mg/day.  

Conclusion: THC use is associated with increased survival time in specific palliative cancer patient cohorts.  

 Citation: Bar-Sela, G., Zalman, D., Bergman, R., & Visel, B. (2019). Cannabis consumption in palliative care patients: A prospective observational study. Supportive Care in Cancer, 27(5), 1759–1766. https://doi.org/10.1007/s00520-018-4441-y

Result: Significant improvements in overall quality of life reported in palliative cancer patients after 6 months of cannabis treatment.

Conclusion: Medical cannabis may significantly improve overall quality of life for palliative cancer patients.

5. Other Symptom Management (Anxiety, Depression, Distress)

Citation: Bar-Sela, G., Zalman, D., Bergman, R., & Visel, B. (2019). Cannabis consumption in palliative care patients: A prospective observational study. Supportive Care in Cancer, 27(5), 1759–1766. https://doi.org/10.1007/s00520-018-4441-y

Result: Significant reductions reported in anxiety, depression, and overall distress scores in palliative cancer patients.

Conclusion: Medical cannabis may significantly improve psychological symptoms and overall distress in palliative cancer patients.  

Citation: Swift, R. M., & Hurd, Y. L. (2011). Cannabidiol (CBD) as a promising anti-addiction treatment. Neuropharmacology, 61(8), 1129–1134. https://doi.org/10.1016/j.neuropharm.2011.08.019

Result: Review discusses the potential of CBD in reducing anxiety and other related symptoms.  

Conclusion: CBD has shown promise for managing some psychological distress.

Important considerations include the variability between individuals, product variations, potential drug interactions, and the general need for more high quality controlled studies.

Breast CA – New: 310K, T: 4M+ Prostate 299K | 3.4M+ , Colorectal  153K, 1.6M+ Melanoma 100K | 1.3M+,   Endometrial 67K | 900K+ NHL (Lymphoma) – New: 80K, T: 800K+ Bladder CA – New: 83K, T: 720K+ Kidney CA – New: 82K, Total: 600K+  Lung CA – New: 238K, Total: 600K+

Pancreatic CA – New: 66K, Total: 190K+

MORTALITY  - Lung & Bronchus CA– 125K deaths​ Colorectal – 53K Pancreatic – 52K​  Breast – 42K Prostate – 35K

Liver & Intrahepatic Bile Duct Cancer – 30K deaths​

Leukemia – 23,090 deaths​ Non-Hodgkin Lymphoma – 20,140 deaths​ Bladder Cancer – 16,840 deaths​ 

Kidney & Renal Pelvis Cancer – 14,390 deaths

1. Chronic Pain

Citation 1
National Academies of Sciences, Engineering, and Medicine. (2017). The health effects of cannabis and cannabinoids. The National Academies Press. https://doi.org/10.17226/24625
Results: Substantial evidence indicates cannabis is effective for chronic pain relief in adults.
Conclusion: Cannabis is a viable option for managing chronic pain in adults.​

Citation 2 [ Smoked Cannabis ]
Ware, M. A., Wang, T., Shapiro, S., et al. (2010). Smoked cannabis for chronic neuropathic pain: A randomized trial. CMAJ, 182(14), E694–E701. https://doi.org/10.1503/cmaj.091414
Results: Participants experienced a 30% reduction in pain intensity with 9.4% THC cannabis.
Conclusion: Smoked cannabis effectively reduces neuropathic pain intensity.​

2. Reduced Morbidity / Reduced Opioid Doses

Citation 1
Boehnke, K. F., Litinas, E., & Clauw, D. J. (2016). Medical cannabis use is associated with decreased opiate medication use in a retrospective cross-sectional survey of patients with chronic pain. Journal of Pain, 17(6), 739–744. https://doi.org/10.1016/j.jpain.2016.03.002
Results: 64% of chronic pain patients reduced opioid use when using medical cannabis.
Conclusion: Medical cannabis may decrease reliance on opioids for pain management.​

3. ADDITIONAL INFO

Citation 1
Sidney, S., Beck, J. E., Tekawa, I. S., et al. (1997). Marijuana use and mortality. American Journal of Public Health, 87(4), 585–590. https://doi.org/10.2105/AJPH.87.4.585
Results: No increased mortality risk associated with marijuana use in men; slight increase in AIDS-related mortality likely due to confounding factors.
Conclusion: Marijuana use does not significantly affect non-AIDS mortality rates.​PBS: Public Broadcasting Service

Citation 2
Desai, R., Patel, U., Sharma, S., et al. (2019). Recreational marijuana use and acute cardiovascular events: Insights from nationwide inpatient data in the United States. American Journal of Medicine, 132(7), 807–815. https://doi.org/10.1016/j.amjmed.2019.02.015
Results: Cannabis use associated with decreased in-hospital mortality among heart attack patients.
Conclusion: Cannabis use may have a protective effect in acute cardiovascular events.​NORML+1CannaMD+1

RISKS 

Citation
Bleyer, A., Barnes, B., & Alpert, J. S. (2021). Cannabis use and risks of respiratory and all-cause morbidity and mortality: A population-based cohort study. BMJ Open Respiratory Research, 9(1), e001216. https://doi.org/10.1136/bmjresp-2021-001216
Results: Cannabis use associated with increased all-cause emergency room visits and hospitalizations.
Conclusion: Cannabis use may elevate risks of respiratory and overall morbidity.

Concise Outline | Multiple Sclerosis (MS)

Definition: Chronic autoimmune disease affecting the central nervous system (CNS), leading to inflammation, demyelination, and axonal damage.

Neurological Symptoms: Visual disturbances, motor impairment, fatigue, cognitive dysfunction, spasticity.

Diagnostic Criteria:

• Historical Landmark: Charcot (1868) first identified MS.

• Tools: MRI (lesions), cerebrospinal fluid (oligoclonal bands), clinical assessment.

• McDonald Criteria (2001, updates in 2010, 2017): Lesion dissemination over time & space. 

4 Types of MS & Prevalence:

1. Relapsing-Remitting MS (RRMS) ~85% – Periodic attacks, partial/full recovery.

2. Primary Progressive MS (PPMS) ~10-15% – Steady worsening, no distinct relapses.

3. Secondary Progressive MS (SPMS) (Develops from RRMS) – Worsening function after initial relapses.

4. Progressive-Relapsing MS (PRMS) ~5% – Steady decline with acute relapses.

History & Timeline of Autoimmune Disease:

• Pre-1900s: Charcot’s MS characterization (1868), infectious theories.

• 1900–1950s: Autoimmunity recognized (Hashimoto’s, Lupus), autoantibodies discovered.

• 1960s–1980s: T-cell, cytokine discoveries; MRI breakthrough.

• 1990s–2000s: Endocannabinoid system (ECS) discovery (1990), Betaseron FDA approval (1993), MS-cannabis research.

• 2010s: Precision medicine; Ocrevus FDA approval (2017), cannabis acceptance.

• 2020s: Advances in immunotherapy, CB₂ research, microbiome studies.

U.S. States Legalizing Medical Cannabis for MS (Many including …)

• California (1996) – Proposition 215.| Oregon (1998) – Oregon Medical Marijuana Act.

• Maine (1999)  Rhode Island (2006)  New Mexico (2007)

• Georgia (2015) – Haleigh’s Hope Act (Low-THC Oil). 

• Florida (2016) – Amendment 2 (Medical Cannabis).  

Risk Factors for MS:

• Genetics – Family history.

• Environmental – Vitamin D deficiency, viral infections.

• Lifestyle – Smoking, toxin exposure.

• Gut Health – Microbiome imbalances.

• Mental Health – Depression, stress.

Preventative Strategies:

• Vitamin D & Sunlight – Lowers MS risk.

• Anti-Inflammatory Diet – Supports gut and immune health.

• Regular Exercise – Boosts immune resilience.

• Stress Management – Reduces flare-ups.

• Avoid Smoking & Toxins – Lowers inflammation risk.

• Early Screening – Identifies risk factors for intervention.

Treatment Overview:

• Standard Therapies: Interferon Beta, Glatiramer Acetate, Ocrelizumab.

• Emerging Therapies: Stem cells, BTK inhibitors, targeted immunotherapies.

• Cannabis-Based: Sativex (nabiximols), Epidiolex (CBD), personalized cannabis regimens.

Future Directions:

• CRISPR gene-editing. Personalized immunotherapies. Remyelination strategies.

• Expanded cannabis integration.

References:

1. Charcot, J. M. (1868). Histological and clinical studies on MS.

2. McDonald, W. I., et al. (2001). MS diagnostic criteria. Ann Neurol.

3. Hauser, S. L., et al. (2017). Ocrelizumab for MS. N Engl J Med.

4. Compston, A., & Coles, A. (2008). MS review. Lancet.

5. California Prop 215 (1996).

6. New Mexico Compassionate Use Act (2007).

7. Florida Amendment 2 (2016).

8. Georgia Haleigh’s Hope Act (2015).  

9. Also see - https://www.nationalmssociety.org/ | https://pubmed.ncbi.nlm.nih.gov/?term=multiple+sclerosis+cann*  | TerelNewton.com

Concise Outline | Stress

Definition: Physiological or psychological response to demands or pressures, disrupting homeostasis.

Symptoms:

• Psychological: Anxiety, irritability, difficulty concentrating, mood swings.

• Physiological: Increased heart rate, muscle tension, headaches, sleep disturbances.

Diagnostic Considerations:

• Subjective assessment: Self-reported symptoms, life events.

• Physiological markers: Cortisol levels, heart rate variability.

• Psychological evaluations: Anxiety and depression scales.

Types of Stress & Prevalence:

• Acute Stress: Short-term response to immediate threats or challenges.

• Chronic Stress: Prolonged exposure to stressors, leading to sustained physiological activation.

• Episodic Acute Stress: Frequent bouts of acute stress.

History & Timeline of Stress Research:

• Early 20th Century: Cannon's "fight or flight" response, Selye's General Adaptation Syndrome (GAS).

• Mid-20th Century: Lazarus's cognitive appraisal theory, Holmes and Rahe's life events scale.

• Late 20th Century: Allostatic load concept, psychoneuroimmunology studies.

• 21st Century: Focus on the impact of chronic stress on the brain, microbiome, and the development of resilience.

Lifestyle Factors and Stress (Many including…):

• Lack of Sleep: Disrupts hormonal balance and cognitive function.

• Poor Diet: Increases inflammation and reduces resilience.

• Sedentary Lifestyle: Reduces physical and mental well-being.

• Social Isolation: Lack of support networks.

• Substance Abuse: Maladaptive coping mechanisms.

Risk Factors for Stress:

• Genetic Predisposition: Variations in stress response genes.

• Environmental Factors: Exposure to trauma, poverty, or discrimination.

• Personality Traits: Neuroticism, low resilience.

• Occupational Stress: Demanding work environments.

• Relationship Issues: Conflict, lack of support.

Preventative Strategies:

• Regular Exercise: Reduces cortisol, increases endorphins.

• Mindfulness and Meditation: Calms the nervous system.

• Balanced Diet: Supports physiological resilience.

• Adequate Sleep: Promotes hormonal regulation.

• Social Support: Buffers against stress impact.

• Time Management: Reduces feelings of being overwhelmed.

Treatment Overview:

• Cognitive Behavioral Therapy (CBT): Modifies maladaptive thought patterns.

• Stress Management Techniques: Relaxation, deep breathing.

• Medications: Antidepressants, anxiolytics (short-term use).

• Lifestyle Modifications: Exercise, diet, sleep hygiene.

• Medical cannabis (CBD, low-dose THC) shows potential for stress relief, but requires careful consideration and professional guidance.  

Future Directions:

• Personalized Stress Management: Tailored interventions based on individual profiles.

• Neurofeedback and Biofeedback: Training self-regulation of physiological responses.

• Gut-Brain Axis Research: Exploring the role of the microbiome in stress resilience.

• Digital Therapeutics: Apps and online programs for stress reduction.

References:

• Cannon, W. B. (1915). Bodily changes in pain, hunger, fear and rage.

• Selye, H. (1936). A syndrome produced by diverse nocuous agents.

• Lazarus, R. S., & Folkman, S. (1984). Stress, appraisal, and coping.

• Holmes, T. H., & Rahe, R. H. (1967). The social readjustment rating scale.

• McEwen, B. S. (1998). Protective and damaging effects of mediators of stress.

• American Psychological Association. (APA) stress resources.

• National Institute of Mental Health (NIMH) stress information.

• Also see - https://www.apa.org/topics/stress | https://www.nimh.nih.gov/health/topics/stress | General stress and wellness resources.

Concise Outline | Autism Spectrum Disorder (ASD)

Definition: A complex neurodevelopmental disorder characterized by persistent challenges in social communication and social interaction, alongside restricted and repetitive patterns of behavior, interests, or activities.

Core Symptoms/Characteristics:

• Social Communication/Interaction Deficits: Difficulties with social-emotional reciprocity, nonverbal communicative behaviors used for social interaction, and developing/maintaining relationships.  

• 
  

• Restricted, Repetitive Behaviors/Interests/Activities (RRBs): Stereotyped or repetitive motor movements/speech, insistence on sameness/inflexible adherence to routines, highly restricted/fixated interests, hyper- or hypo-reactivity to sensory input.  

• 
  

Diagnostic Criteria:

• Historical Landmarks: Kanner (1943) described "early infantile autism"; Asperger (1944) described "autistic psychopathy".  

• 
  

• Tools: Clinical observation, detailed developmental history, standardized assessments (e.g., ADOS-2, ADI-R).

• Diagnostic Manual: DSM-5 (Diagnostic and Statistical Manual of Mental Disorders, 5th Ed., 2013) – Requires persistent deficits in social communication/interaction AND at least two types of RRBs. Specifies severity levels based on support needed.  

• 
  

Severity Levels (DSM-5) & Prevalence:

• Level 3: Requiring very substantial support.

• Level 2: Requiring substantial support.

• Level 1: Requiring support.

• Prevalence: Approximately 1 in 36 children in the U.S. identified with ASD (CDC, 2023 data). Affects all ethnic and socioeconomic groups.  

• 
  

History & Timeline of Autism Understanding:

• Pre-1940s: Not distinctly recognized.

• 1940s–1970s: Kanner & Asperger's initial descriptions; psychoanalytic theories (e.g., "refrigerator mother" - later discredited).

• 1980s–1990s: Recognized as a developmental disorder (DSM-III); shift towards biological/genetic basis; increased research.

• 2000s: Rapid increase in prevalence estimates and public awareness; focus on early intervention.

• 2010s: DSM-5 consolidates previous diagnoses (Autistic Disorder, Asperger's, PDD-NOS) into ASD; genetic research expands; initial research into cannabinoids for ASD symptoms.  

• 
  

• 2020s: Focus on neurodiversity, personalized interventions, co-occurring conditions, continued genetic and biomarker research.

U.S. States Legalizing Medical Cannabis for Autism (Selected Examples Including...): (Note: Laws vary; some list ASD specifically, others allow it via physician discretion under broader categories or for specific symptoms.)

• Delaware (2011, added Autism later)

• Minnesota (2014, added Autism 2018)

• Georgia (2015) – Haleigh’s Hope Act (Low-THC Oil for severe autism or patients >18).  

• 
  

• Pennsylvania (2016, added Autism 2018)

• Florida (2016) – Amendment 2 (Not explicitly listed, but often qualifies via physician determination under "medical condition of the same kind or class" or for co-occurring conditions like seizures).  

• 
  

• Texas (2015, expanded 2019/2021) – Compassionate Use Program (Low-THC for specific conditions including Autism).

Risk Factors for ASD:

• Genetics: Strongest factor; numerous genes implicated; higher risk with family history or certain genetic conditions (e.g., Fragile X, Tuberous Sclerosis).

• Environmental/Prenatal: Advanced parental age, prenatal exposure to certain medications (e.g., valproic acid) or infections, complications during birth, low birth weight. (Note: No reliable evidence links vaccines to ASD).

• Neurological: Differences in brain structure and function.

Supportive Strategies & Interventions:

• Early Intervention: Crucial; includes behavioral therapies (ABA), speech therapy, occupational therapy.  

• 
  

• Behavioral Approaches: Applied Behavior Analysis (ABA), Pivotal Response Training (PRT).

• Educational Support: Specialized instruction, IEPs (Individualized Education Programs).

• Social Skills Training: Programs to improve interaction and understanding social cues.  

• 
  

• Sensory Integration Therapy: Addressing sensory sensitivities.

• Family Support & Training: Resources and strategies for caregivers.

Treatment/Intervention Overview:

• Standard Therapies: No cure; focus on managing symptoms and maximizing function via behavioral, educational, and developmental therapies. Medications (e.g., Risperidone, Aripiprazole) FDA-approved for irritability associated with ASD; others target co-occurring conditions (ADHD, anxiety, epilepsy).  

• 
  

• Emerging Approaches: Variations in behavioral therapies, technology-assisted interventions.

• Cannabis-Based: Research primarily focuses on CBD for co-occurring symptoms like seizures, anxiety, aggression, and sleep problems. Clinical trials are ongoing (e.g., studies by Aran et al.).

Future Directions:

• Improved early detection and diagnostic tools.

• Biomarker identification for tailored interventions.

• Deeper understanding of ASD's heterogeneity and underlying biology.

• Development of targeted pharmacological treatments.

• Continued research into cannabis-based therapies (CBD, other cannabinoids) for specific symptoms.

• Emphasis on neurodiversity acceptance and improving quality of life across the lifespan.

References:

• Kanner, L. (1943). Autistic disturbances of affective contact. Nervous Child.  

• 
  

• Asperger, H. (1944). Die ‘Autistischen Psychopathen’ im Kindesalter. Archiv für Psychiatrie und Nervenkrankheiten.  

• 
  

• American Psychiatric Association. (2013). Diagnostic and Statistical Manual of Mental Disorders (5th ed.).

• CDC Autism Data and Statistics: https://www.cdc.gov/ncbddd/autism/data.html

• Autism Speaks: https://www.autismspeaks.org/

• Autism Research Institute (ARI): https://www.autism.org/

• Bar-Lev Schleider, L., et al. (2019). Real life Experience of Medical Cannabis Treatment in Autism. Sci Rep.

• Also see - https://pubmed.ncbi.nlm.nih.gov/?term=autism+spectrum+disorder+cannab*

Concise Outline | Parkinson's Disease (PD)

Definition: Progressive neurodegenerative disorder affecting movement, due to loss of dopamine-producing neurons.

Symptoms:

• Motor: Tremor, rigidity, bradykinesia (slow movement), postural instability.

• Non-Motor: Depression, anxiety, sleep disturbances, cognitive changes, autonomic dysfunction.

Diagnostic Criteria:

• Clinical assessment: Presence of cardinal motor symptoms.

• DaTscan: Imaging to assess dopamine transporter levels.

• Levodopa response: Improvement in symptoms with levodopa.

Types of PD & Prevalence:

• Idiopathic PD: Most common, cause unknown.

• Atypical Parkinsonism: Other neurodegenerative diseases with Parkinsonian features.

• Early-Onset PD: Onset before age 50.

History & Timeline of PD Research:

• 1817: James Parkinson's "An Essay on the Shaking Palsy."

• 1960s: Discovery of dopamine's role, levodopa therapy.

• 1980s-1990s: Development of dopamine agonists, deep brain stimulation (DBS).

• 21st Century: Genetic research, non-motor symptom focus, neuroprotection studies.

Lifestyle Factors and PD (Many including…):

• Exercise: Neuroprotective effects, symptom management.

• Nutrition: Balanced diet, potential benefits of certain nutrients.

• Sleep Hygiene: Addressing sleep disturbances.

• Stress Management: Reducing symptom exacerbation.

• Social Engagement: Combating isolation and depression.

Risk Factors for PD:

• Age: Primary risk factor.

• Genetics: Mutations in specific genes.

• Environmental Toxins: Pesticide exposure.

• Head Trauma: Potential link to increased risk.

• Male Gender: Slightly higher prevalence.

Preventative Strategies:

• Regular Exercise: May reduce risk.

• Healthy Diet: Antioxidant-rich foods.

• Avoidance of Toxins: Limiting exposure to pesticides.

• Managing Comorbidities: Addressing conditions like hypertension.

Treatment Overview:

• Levodopa: Gold standard for motor symptom management.

• Dopamine Agonists: Alternative or adjunct to levodopa.

• Deep Brain Stimulation (DBS): Surgical intervention for advanced PD.

• Physical Therapy: Improving mobility and balance.

• Medical cannabis: potential for non motor symptom relief, but more research is needed.

Future Directions:

• Neuroprotective Therapies: Slowing disease progression.

• Gene Therapy: Addressing underlying genetic causes.

• Stem Cell Therapy: Regenerating dopamine-producing neurons.

• Personalized Medicine: Tailoring treatments to individual needs.

References:

• Parkinson, J. (1817). An Essay on the Shaking Palsy.

• Lang, A. E., & Lozano, A. M. (1998). Parkinson's disease. N Engl J Med.

• Poewe, W. (2008). Clinical aspects of Parkinson's disease. Mov Disord.

• National Institute of Neurological Disorders and Stroke (NINDS) PD information.

• The Michael J. Fox Foundation for Parkinson's Research.

• Also see - https://www.ninds.nih.gov/ | https://www.michaeljfox.org/ | General Parkinson's Disease resources.

Concise Outline | Migraines

Definition: Recurrent, moderate to severe headaches often accompanied by other neurological symptoms.

Symptoms:

• Head pain: Throbbing, unilateral.

• Aura: Visual, sensory, or motor disturbances.

• Nausea/vomiting, photophobia, phonophobia.

Diagnostic Criteria:

• International Headache Society criteria.

• Frequency, duration, and characteristics of headaches.

• Exclusion of other causes.

Types of Migraines & Prevalence:

• Migraine with aura (classical migraine).

• Migraine without aura (common migraine).

• Chronic migraine.

• Vestibular migraine.

History & Timeline of Migraine Research:

• Ancient texts: Descriptions of migraine-like headaches.

• 19th century: Recognition as a distinct neurological disorder.

• 20th century: Serotonin's role, triptan development.

• 21st century: CGRP pathway, gepant and ditan drugs.

Lifestyle Factors and Migraines (Many including…):

• Sleep disturbances, stress, dietary triggers (e.g., caffeine, alcohol).

• Hormonal fluctuations, environmental changes.

• Dehydration, skipping meals.

Risk Factors for Migraines:

• Family history, female gender, hormonal changes.

• Stress, certain foods, sensory stimuli.

Preventative Strategies:

• Identifying and avoiding triggers.

• Regular sleep, stress management.

• Prophylactic medications (beta-blockers, antidepressants).

Treatment Overview:

• Acute medications: Triptans, NSAIDs, CGRP antagonists.

• Preventative medications.

• Lifestyle modifications, biofeedback.

• Medical cannabis: Potential for pain and symptom relief, more research needed.

Future Directions:

• Personalized medicine, gene therapy, novel CGRP-targeted therapies.

• Improved understanding of neuroinflammation.

References:

• International Headache Society (IHS) guidelines.

• Headache journal publications.

• National Institute of Neurological Disorders and Stroke (NINDS) migraine information.

Concise Outline | Irritable Bowel Syndrome (IBS)

Definition: Chronic gastrointestinal disorder characterized by abdominal pain, bloating, and altered bowel habits.

Symptoms:

• Abdominal pain/cramping, bloating, gas.

• Diarrhea-predominant (IBS-D), constipation-predominant (IBS-C), mixed (IBS-M).

• Changes in stool frequency and consistency.

Diagnostic Criteria:

• Rome IV criteria.

• Symptom duration and frequency.

• Exclusion of other gastrointestinal diseases.

Types of IBS & Prevalence:

• IBS-D, IBS-C, IBS-M, IBS-Unspecified.

History & Timeline of IBS Research:

• Early descriptions of functional bowel disorders.

• 20th century: Recognition as a distinct clinical entity.

• 21st century: Gut-brain axis, microbiome research.

Lifestyle Factors and IBS (Many including…):

• Stress, diet (FODMAPs), gut microbiome imbalances.

• Psychological factors (anxiety, depression).

• Food sensitivities.

Risk Factors for IBS:

• Female gender, prior gastrointestinal infections.

• Stressful life events, psychological disorders.

Preventative Strategies:

• Stress management, dietary modifications (low-FODMAP diet).

• Probiotics, prebiotics.

• Regular exercise.

Treatment Overview:

• Dietary changes, fiber supplements.

• Antispasmodics, antidiarrheals, laxatives.

• Psychological therapies (CBT, hypnotherapy).

• Medical cannabis: Potential for symptom relief, more research needed.

Future Directions:

• Microbiome-targeted therapies, gut-brain axis modulation.

• Personalized dietary interventions.

References:

• Rome Foundation criteria.

• Gastroenterology journal publications.

• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) IBS information.

Endocannabinoid System (ECS) Deficiency Note:

• Migraines, IBS, and Fibromyalgia have shown some evidence of association with a potential Endocannabinoid System Deficiency (Clinical Endocannabinoid Deficiency - CECD). This theory suggests that some individuals may have a lower than optimal function of their ECS, which can contribute to the development or severity of these conditions.

• The ECS plays a role in pain modulation, gut motility, and neuroinflammation, all of which are involved in these conditions.

• Research is ongoing to further explore the relationship between ECS function and these disorders, and to evaluate the therapeutic potential of cannabinoids.

Concise Outline | Mental Health

Definition: State of well-being where individuals realize their abilities, cope with stressors, and contribute to their community.

Symptoms:

• Psychological: Anxiety, depression, mood swings, cognitive impairment, psychosis.

• Behavioral: Social withdrawal, substance abuse, changes in sleep/appetite.

Diagnostic Criteria:

• DSM-5 (Diagnostic and Statistical Manual of Mental Disorders).

• Clinical interviews, psychological evaluations, symptom checklists.

• Neuroimaging (in some cases).

Common Mental Health Conditions & Prevalence:

• Depression (~5% global prevalence).

• Anxiety Disorders (~4% global prevalence).

• Bipolar Disorder (~1% global prevalence).

• Schizophrenia (~1% global prevalence).

History & Timeline of Mental Health Treatment:

• Pre-1900s: Moral treatment, asylums.

• 1900–1950s: Psychoanalysis, electroconvulsive therapy (ECT).

• 1960s–1980s: Antipsychotics, antidepressants, community mental health.

• 1990s–2000s: Selective serotonin reuptake inhibitors (SSRIs), cognitive behavioral therapy (CBT).

• 2010s-2020s: Precision psychiatry, digital mental health, neuromodulation, cannabis research.

U.S. States Legalizing Medical Cannabis for Mental Health (Varies, some including…):

• Many states with medical cannabis programs allow it for conditions like PTSD, anxiety, and depression, contingent on qualifying criteria and physician recommendations.

• Specific qualifying conditions vary widely by state.

Risk Factors for Mental Health Conditions:

• Genetics – Family history.

• Environmental – Trauma, stress, socioeconomic factors.

• Biological – Neurotransmitter imbalances, brain abnormalities.

• Substance Use – Drug and alcohol abuse.

Preventative Strategies:

• Stress management, coping skills.

• Healthy lifestyle (diet, exercise, sleep).

• Social support, community engagement.

• Early intervention, mental health literacy.

Treatment Overview:

• Psychotherapy (CBT, DBT, etc.).

• Medications (antidepressants, antipsychotics, anxiolytics).

• Neuromodulation (ECT, TMS).

• Cannabis-Based:

  • CBD: Potential for anxiety and PTSD symptom relief; research ongoing.

  • THC: Complex relationship; low doses may alleviate some symptoms, but high doses can exacerbate anxiety/psychosis.

  • Clinical Considerations: Requires careful monitoring, professional guidance, and personalized regimens due to potential interactions and risks.

Future Directions:

• Personalized psychiatry, biomarker identification.

• Digital therapeutics, AI-driven interventions.

• Gut-brain axis research, microbiome interventions.

• Expanded research into cannabis's therapeutic potential.

References:

• American Psychiatric Association (APA) DSM-5.

• World Health Organization (WHO) Mental Health Reports.

• National Institute of Mental Health (NIMH).

• APA Practice Guidelines.

• Peer reviewed research on cannabis and mental health conditions.

• State-specific medical cannabis program guidelines.

• Also see - https://www.nimh.nih.gov/ | https://www.who.int/mental_health/en/ | General Mental Health Resources.

Breaking the Pill Cycle: Medical Cannabis as a Remedy for Polypharmacy

Author: Terel Newton, MD Florida Medical Director, Trulieve Medical Director, Total Pain Relief, LLC and Interventional Pain Consultant

Slide 1: Title Slide

• Title: Breaking the Pill Cycle: Medical Cannabis as a Remedy for Polypharmacy

• Author: Terel Newton, MD

• Affiliations: Florida Medical Director, Trulieve; Medical Director, Total Pain Relief, LLC and Interventional Pain Consultant

Slide 2: Introduction: The Challenge of Polypharmacy

• Definition: Polypharmacy = concurrent use of multiple medications.

• Context: Multiple drugs for one condition OR drugs to treat side effects of others.

• Problem Statement: Significant concern, especially among older adults.

• Goal: Exploring medical cannabis as a potential strategy to reduce medication burden.

Slide 3: Polypharmacy: Scope of the Problem

• Increased Risks: Adverse drug events, drug interactions, non-adherence.

• Specific Concerns for Older Adults: Increased risk of falls, cognitive impairment, hospitalization, decreased quality of life.

Slide 4: Polypharmacy and Frailty in Older Adults

• Define Frailty: Geriatric syndrome - decreased physiological reserves, increased vulnerability.

• The Link: Systematic review found significant association between polypharmacy and frailty.

  • 16/18 cross-sectional & 5/7 longitudinal studies showed correlation.  

• Implication: Polypharmacy may be a contributor to frailty.  

Slide 5: The Need for Medication Reduction Strategies

• Goal: Reduce medication burden where risks outweigh benefits.

• Patient & Physician Goals: Many seek to replace or reduce conventional medicines.

• Potential Benefits of Deprescribing: Improved quality of life, reduced psychological distress , decreased risk of adverse events.  

Slide 6: Medical Cannabis: A Potential Alternative?

• Growing Acceptance: Increasing legalization and patient use.

• Florida Context: Over 900,000 qualified patients with active ID cards as of March 2025.  

• Patient Interest: Often driven by desire to reduce pharmaceuticals, perceived safety, and dissatisfaction with current treatments.  

Slide 7: Understanding the Endocannabinoid System (ECS)

• Brief Overview: Body's natural cannabinoid system.

• Role: Modulates pain, mood, sleep, appetite, inflammation, memory, etc..  

• Mechanism: How cannabinoids like THC and CBD interact with the ECS (CB1/CB2 receptors).  

Slide 8: Key Cannabinoids: THC and CBD

• Delta-9-Tetrahydrocannabinol (THC):

  • Primary psychoactive component.  

  • Therapeutic effects: Analgesia, anti-nausea, appetite stimulation.  

• Cannabidiol (CBD):

  • Non-intoxicating.  

  • Therapeutic effects: Analgesia, anti-inflammatory, anxiolytic, anti-seizure.  

  • May modulate THC effects.  

Slide 9: Why Patients Consider Cannabis for Medication Reduction

• Desire to Reduce Opioids/Other Meds: Concerns about dependence, side effects, stigma.  

• Perceived Inefficacy/Side Effects of Current Meds: Pain poorly controlled, sedation, constipation, cognitive issues.  

• Perception of Cannabis: Safer, "natural" alternative.  

• Hope for Better Symptom Control: Pain, sleep, aniety.  

Slide 10: Cannabis for Opioid Reduction: Rationale & Mecanisms

• Opioid & Endocannabinoid System Overlap: Both involved in pain modulation.  

• Preclinical Evidence: Synergistic analgesic effects (THC + Opioids).  

• Potential Mechanisms: Direct pain modulation, anti-inflammatory effects, symptom cluster relief (nausea, anxiety, insomnia).  

• Harm Reduction Perspective: Higher therapeutic index than opioids, lower respiratory depression risk.  

Slide 11: Cannabis for Opioid Reduction: Observational Evidence

• Significant Reductions Reported: 64-75% reduction in opioid dosage reported in some studies when combined with MC.  

• Opioid Substitution: 32-59.3% reported substituting cannabis for opioids.  

• Specific Study Examples:

  • Michigan dispensary survey: 64% reduction.  

  • Florida study: 79% reported cessation/reduction.  

  • Canadian TOPS study: Opioid use dropped from 28% to 11% over 6 months.  

  • Prospective study: Avg. MME reduction 67-73%.  

Slide 12: Cannabis for Opioid Reduction: Evidence Caveats

• Observational Data Limitations: High risk of bias, confounding factors, selection bias, reliance on self-report.  

• Causality Cannot Be Inferred.  

• RCT Limitations: Often designed not to assess opioid-sparing effects (instructed to maintain dose).  

• Certainty of Evidence: Rated low to very low in systematic reviews.  

Slide 13: Case Report 1: Post-Transplant Complex Pain  

• Patient: 57yo Male, post-liver transplant, chronic abdominal pain pre-op.

• Challenge: Difficult opioid wean post-op (up to 30mg/day hydromorphone).

• Intervention: Medical cannabis initiated 6 weeks post-op.

• Outcome: Successfully tapered to 6mg/day hydromorphone (~80% reduction); excellent functional status reported.

Slide 14: Case Report 2: High-Dose Opioids after TBI  

• Patient: 43yo Female, TBI history, chronic head/neck/shoulder pain (VAS 8/10).

• History: >10 years on opioids, up to 150 MME/day (MS Contin + Morphine IR).

• Intervention: Structured opioid wean + Harlequin vape (2:1 CBD:THC, 5mg/day).

• Outcome: 100% opioid cessation over ~5 weeks; Pain VAS reduced to 2/10 (sustained 6 mo); No cannabis side effects reported.

Slide 15: Case Report 3: Older Adult with Chronic Pain  

• Patient: 72yo Female, chronic pain (OA, scleroderma, scoliosis).

• History: ~10 years on opioids, 75-90 MME/day (Oxycodone).

• Intervention: 1:1 CBD:THC sublingual tincture, titrated to 6mg CBD/6mg THC TID (36mg total/day).

• Outcome: 100% opioid cessation over ~1 year; Pain VAS reduced 8/10 to 6/10; Improved sleep; Dizziness with higher THC trial.

Slide 16: Cannabis for Benzodiazepine (BZD) Reduction: Rationale

• Problems with Long-Term BZD Use: Dependence, tolerance, side effects (sedation, cognitive impairment, falls), difficult withdrawal.  

• Potential Role for Cannabis:

  • Symptom substitution (anxiety, insomnia relief via CBD/THC).  

  • Possible GABAergic modulation.  

Slide 17: Cannabis for Benzodiazepine Reduction: Evidence & Concerns

• Observational Data: Purcell et al. retrospective study - 45.2% BZD discontinuation rate after ~6 months of MC use.  

• Major Limitations: Retrospective, self-reported, no causality, lack of detail on BZD use/tapering protocol, potential bias.  

• Safety Concerns: Paradoxical anxiety from THC, dependence substitution, risk of unsafe/abrupt discontinuation if cannabis only masks withdrawal.  

Slide 18: Cannabis for Anticonvulsant (AED) Reduction: Context

• Established Evidence: Pharmaceutical CBD (Epidiolex) approved for Dravet Syndrome, Lennox-Gastaut Syndrome, Tuberous Sclerosis Complex based on RCTs.  

• Mechanism: Likely multifactorial, distinct from THC, involves calcium modulation, TRPV1, etc..  

Slide 19: Cannabis for Anticonvulsant Reduction: Tapering Evidence

• Potential for AED Reduction: Suggested by open-label extensions, surveys, retrospective studies (often using artisanal CBD).  

• Case Reports: Charlotte Figi (Dravet, CBD extract monotherapy) ; Masataka infant case (EIEE, CBD monotherapy achieved).  

• Caveats:

  • Variability/quality concerns with artisanal products.  

  • CBD-Clobazam interaction (CYP inhibition) may confound results.  

Slide 20: Cannabis for Antidepressant Reduction

• Evidence Gap: Very limited direct evidence or case reports on using cannabis to facilitate antidepressant tapering.  

• Indirect Evidence: Potential for symptom management (anxiety/depression) ; Case reports of concurrent use (not for tapering).  

• Major Concern: Pharmacokinetic interactions - CBD/THC inhibit CYP enzymes (2C19, 2D6) metabolizing many SSRIs, potentially increasing antidepressant levels and side effects.  

Slide 21: Impact on Quality of Life (QoL)

• Patient Reports: Improved QoL often cited as benefit alongside medication reduction.  

• Prospective Studies:

  • Multi-site study (>50yo): Reduced/discontinued meds associated with QoL improvements.  

  • TOPS study: Significant improvements in WHOQOL-BREF domains (physical, psychological, social, environmental) with MC use, including among those reducing opioids/BZDs.  

  • Florida study: Improvements in bodily pain, physical/social functioning.  

Slide 22: Patient Perspectives & Motivations

• Why Use Cannabis? Dissatisfaction with current meds, desire to reduce pharmaceuticals (esp. opioids), perceived safety/natural alternative, hope for better symptom control.  

• Experiences: Often positive (pain relief, sleep, mood), but side effects or lack of efficacy lead some to discontinue.  

• Preferences: Need for experimentation, favor balanced/CBD products, oral/sublingual routes often preferred for sustained effects.  

Slide 23: Barriers from the Patient Perspective

• Cost: Often out-of-pocket, significant barrier.  

• Stigma: Social stigma persists despite legalization.  

• Access: Finding knowledgeable providers, navigating regulations.  

• Lack of Guidance: Insufficient clinical advice on products, dosing, leading to self-experimentation.  

Slide 24: Cannabis Regimens in Practice

• Heterogeneity: Wide variety of products (flower, oils, capsules), ratios (THC:CBD), routes (inhaled, oral, topical).  

• Dosing Strategy: "Start low, go slow" consensus, especially for THC.

  • Initial CBD: 5-20mg.  

  • Initial THC: 0.5-3mg or 2.5-5mg.  

  • Titration: Gradual increase based on response/tolerability.  

• Route Choice: Oral/sublingual preferred for control; Inhalation for rapid onset.  

Slide 25: Safety Considerations: Cannabis Adverse Effects

• Common: Dizziness, drowsiness, fatigue, dry mouth, increased appetite, GI issues (diarrhea with CBD).  

• Cognitive: Impaired concentration, memory, coordination.  

• Psychiatric: Anxiety, paranoia (esp. high THC); Risk of psychosis exacerbation (contraindication).  

• Cardiovascular: Tachycardia.  

Slide 26: Safety Considerations: Challenges of Tapering Itself

• Withdrawal Syndromes are Real:

  • Opioids: Pain, flu-like symptoms, GI upset, anxiety, insomnia.  

  • Benzodiazepines: Severe anxiety/insomnia, restlessness, potential seizures.  

  • Antidepressants: Dizziness, nausea, 'brain zaps', mood changes.  

• Patient Fears: Uncontrolled pain/symptoms, loss of function, relapse.  

• Risks of Tapering: Worsening symptoms, dropout, potential harms if done inappropriately.  

Slide 27: Safety Considerations: Cannabis Withdrawal Syndrome (CWS)

• Potential for Dependence Substitution.  

• 
  

• Prevalence: Affects ~47-59% of regular/dependent users.  

• 
  

• Symptoms: Irritability, anxiety, sleep issues, appetite changes, restlessness, mood changes, physical symptoms (headache, sweating, etc.).  

• 
  

• Timeline: Onset 1-2 days, peak 2-6 days, resolve 1-3 weeks (sleep issues may persist).  

• 
  

• Significance: Can undermine cessation attempts, precipitate relapse.  

• 
  

Slide 28: Clinical Considerations for Florida Practitioners

• Acknowledge Patient Interest & Goals: Open discussion is key.

• Shared Decision-Making: Discuss limited evidence, potential benefits AND risks (side effects, interactions, CWS).

• Cautious Approach: Start low, go slow, monitor closely for efficacy and adverse events.

• Comprehensive Care: Cannabis is an adjunct, not sole solution; integrate with behavioral support, manage comorbidities.

• Florida Landscape: High patient numbers , need for informed guidance within state regulations.  

• 
  

Slide 29: Future Directions & Conclusion

• Research Needs: High-quality RCTs on tapering, comparative effectiveness, long-term outcomes, mechanisms.

• Conclusion:

  • Polypharmacy is a significant issue, especially for older adults.

  • Medical cannabis shows potential based on observational data, case reports, and patient perspectives to reduce medication burden (opioids, BZDs, possibly AEDs) and improve QoL.

  • Evidence is currently limited/low quality; causality not established.

  • Risks (side effects, interactions, CWS) must be considered.

  • Requires individualized, cautious approach and shared decision-making.

Slide 30: Q&A / Contact Information

• Questions?

• Contact: Terel Newton, MD (Include contact details if desired)