I. Introduction (5 minutes)

Pain affects millions globally, with medical cannabis emerging as a potential adjunct therapy. Pharmacists' expertise is crucial in navigating its therapeutic use, ensuring safety, and managing risks. This presentation explores the pharmacodynamics, pharmacokinetics, clinical applications, and pharmacist responsibilities in medical cannabis for pain management.

• Prior slides  HISTORY TIMELINE

II. Basics of Medical Cannabis (10 minutes)

Cannabis Plant and Chemical Composition:
Cannabinoids include Δ9-tetrahydrocannabinol (THC), a partial agonist of CB1/CB2 receptors, and cannabidiol (CBD), which acts indirectly by modulating receptor activity (e.g., allosteric modulation). Terpenes contribute to the "entourage effect," influencing analgesia and inflammation.

• Total Cannabinoids  | Most common products - THC, CBD, 1:1 , Ratios, CBN  || 

• Terpenes - image || B-Myrcene Study 

Endocannabinoid System (ECS):

• ECS = CB1 (CNS) and CB2 (immune system) receptors, endogenous ligands (AEA, 2-AG), and enzymes (NAPE-PLD, FAAH, MAGL).

• Pain signal ↑ → AEA/2-AG release ↑ → CB1 activation ↓ nociceptive transmission and CB2 activation ↓ cytokine-mediated inflammation.

• Prior slides ;   ECS ORGANS / ECS DEF.

Pharmacodynamics:

• THC binds CB1 (GPCR) → cAMP ↓ → neuronal excitability ↓.

• CBD inhibits FAAH → AEA breakdown ↓ → prolonged CB1 activation.

• CBD modulates TRPV1 and PPARγ → anti-inflammatory effects.

• Prior slides || PAIN PATHWAY -- RECEPTORS -- 

Pharmacokinetics:

• THC: Oral bioavailability 6–20%, Tmax = 2–4 hours, hepatic metabolism (CYP2C9, CYP3A4), t1/2 = 25–36 hours.

• CBD: Oral bioavailability 6–19%, Tmax = 2–6 hours, hepatic metabolism (CYP3A4, CYP2C19), t1/2 = 18–32 hours.

• Prior slides  // EPIDIOLEX - AUC 

III. Evidence-Based Role of Cannabis in Pain Management (15 minutes)

Clinical Studies:

• 2020 Pain Medicine study: THC/CBD combination ↓ pain severity, ↑ quality of life in chronic pain.

• 2021 The BMJ: Small improvements in chronic pain relief; moderate-to-low certainty evidence.

Neuropathic Pain:

• Pain signal ↑ → peripheral sensitization (voltage-gated sodium channel activity ↑). THC activation of CB1 ↓ neurotransmitter release (e.g., glutamate) → pain signaling ↓.

• CBD: TRPV1 activation → nociceptor sensitization ↓.

Opioid-Sparing Effects:

• THC/CBD adjunctive use with opioids → μ-opioid receptor desensitization ↓ → opioid requirement ↓.

• 2021 BMJ Open: Observational studies suggest opioid dose ↓ with cannabis; randomized controlled trial evidence limited.

Anti-inflammatory Pathways:

• Chronic pain → pro-inflammatory cytokines (TNF-α, IL-1β) ↑. CB2 activation ↓ cytokine release.

• CBD inhibition of NF-κB → inflammation ↓.

IV. Cannabis Formulations, Dosing, and Pharmacology (10 minutes)

Formulations:

• Products: Tinctures, capsules, edibles, inhalation, topicals.

• THC
  ratios tailored for pain (e.g., 1:1 for balanced effects, high-CBD for inflammatory conditions).

• Prior slides  //  GILDA'S CLUB - ONSET. 

Dosing Guidelines:

• Start low, go slow: THC starting dose ~1–2.5 mg, titrated based on tolerance and efficacy.

• CBD: Initial dose ~10–20 mg/day, titrated upward

• Prior slides  -NEW = REVIEW FDA APPROVED MEDS / SATIVEX .

Pharmacodynamics of Interactions:

• THC: Additive sedation with benzodiazepines, synergistic effects with opioids (respiratory depression risk).

• CBD: P450 enzyme inhibition (CYP3A4, CYP2C19) → ↑ levels of warfarin, clobazam, anti-epileptics.

Pharmacokinetics of Interactions:

• THC metabolized via CYP2C9, CYP3A4 → drug levels affected by inducers (e.g., rifampin ↓ THC) and inhibitors (e.g., ketoconazole ↑ THC).

• CBD ↑ clobazam active metabolite (N-desmethylclobazam) via CYP2C19 inhibition.

• Prior slides

V. Safety and Adverse Effects (10 minutes)

Adverse Effects:

• THC: Common = dizziness, dry mouth, tachycardia; Rare = psychosis, cannabis hyperemesis syndrome.

• CBD: Common = diarrhea, fatigue; Rare = hepatotoxicity (dose-related, especially with anti-epileptic drugs).

• Prior slides; GILDA'S CLUB 

Drug-Drug Interactions:

• THC + sedatives (e.g., benzodiazepines) → ↑ CNS depression.

• CBD + warfarin → ↑ INR (CYP2C19 inhibition).

• THC/CBD + SSRIs → ↑ serotonin syndrome risk (serotonergic modulation).

Patient Counseling on Safety:

• Avoid driving/operating machinery.

• Proper storage to prevent pediatric access.

VI. Role of the Pharmacist (10 minutes)

Counseling Responsibilities:

• Educate on delayed onset with oral cannabis (Tmax = 2–4 hours) to prevent overdose.

• Monitor for efficacy using patient-reported outcomes (pain scales, QoL assessments).

Managing Drug-Drug Interactions:

• Adjust doses of CYP450-metabolized drugs (e.g., antiepileptics, warfarin).

• Avoid polypharmacy with sedatives unless carefully monitored.

Collaboration with Providers:

• Work with prescribers to integrate cannabis into multimodal pain management strategies.

VII. Case Studies and Application (5 minutes)

Case 1: Chronic Neuropathic Pain

• Patient with diabetic neuropathy started on THC
  1:1 tincture at 2.5 mg BID. After 4 weeks: Pain scale ↓ by 50%, gabapentin dose ↓ by 25%.

Case 2: Opioid Dose Reduction

• Cancer pain patient on 30 mg morphine TID. Added THC (2 mg QHS) + CBD (10 mg BID). Morphine dose tapered by 50% in 6 weeks without pain escalation.

VIII. Conclusion and Key Takeaways (5 minutes)

Medical cannabis, through ECS modulation, reduces nociceptive signaling and inflammation. THC and CBD offer potential opioid-sparing effects but require careful monitoring of pharmacokinetics and drug-drug interactions. Pharmacists must balance evidence-based use with safety counseling, ensuring patient-centered care while mitigating risks. Continued research and regulatory evolution will enhance the integration of medical cannabis into pain management.

References:

• 2020 Pain Medicine: https://academic.oup.com

• 2021 The BMJ: https://www.bmj.com

• 2021 BMJ Open: https://bmjopen.bmj.com

• 2022 BMJ Open: https://bmjopen.bmj.com

• Pain Management Nursing: https://www.painmanagementnursing.org

Chronological Overview of Medical Cannabis Laws in Texas

2015: Establishment of the Texas Compassionate Use Program (CUP)

• The Texas Legislature passed the Compassionate Use Act (Senate Bill 339), creating the CUP.

• Initially, the program allowed the use of low-THC cannabis (≤0.5% THC) for patients with intractable epilepsy.

2019: Expansion of CUP Under House Bill 3703

• The list of qualifying conditions was expanded to include:

  • Multiple sclerosis

  • Spasticity

  • Autism

  • Terminal cancer

  • Incurable neurodegenerative diseases

• THC limit remained at 0.5%.

2021: Further Expansion Under House Bill 1535

• The THC limit for medical cannabis was increased from 0.5% to 1%.

• Qualifying conditions were expanded to include:

  • Post-traumatic stress disorder (PTSD)

  • Cancer (broadened beyond terminal cancer to include all cancer types)

2022–2023: Local Decriminalization Efforts

• Cities such as Austin, San Marcos, and Denton passed ordinances decriminalizing possession of small amounts of marijuana, though this does not change state law.

• Local measures reflected shifting public attitudes toward cannabis reform.

November 2024: Introduction of Adult-Use Cannabis Legalization Bill

• A Texas lawmaker introduced a bill to legalize cannabis for adult use, including provisions for regulation and taxation.

• The bill proposes the establishment of a recreational cannabis market, but it requires approval in the 2025 legislative session.

Current Status of Medical Cannabis in Texas

• Texas Compassionate Use Program:

  • Allows use of low-THC cannabis (≤1% THC) for specific medical conditions.

  • Physicians registered with the program can prescribe cannabis to permanent Texas residents.

  • No age restrictions exist for qualifying patients.

• Qualifying Conditions (as of 2024):

  • Epilepsy, seizure disorders

  • Multiple sclerosis

  • Spasticity

  • Autism

  • PTSD

  • Cancer (all types)

  • Amyotrophic lateral sclerosis (ALS)

  • Incurable neurodegenerative diseases

• Limitations:

  • Recreational cannabis remains illegal.

  • Statewide legalization and expanded access depend on future legislative action.

additional resources ... 

Pain is a pervasive global health issue, significantly impacting individuals' quality of life and contributing to substantial healthcare burdens. In the United States, the opioid epidemic has further complicated pain management strategies. Pharmacists play a crucial role in integrating medical cannabis as an adjunct therapy, ensuring its safe and effective use.

Global Pain Statistics:

• Approximately 1.71 billion people worldwide suffer from musculoskeletal conditions, including low back pain, neck pain, and osteoarthritis.
  World Health Organization

• Chronic pain affects about 20% of adults globally, with 10% newly diagnosed each year.
  BMC Public Health

United States Pain and Opioid Epidemic Statistics:

• Chronic pain affects an estimated 20.4% of U.S. adults, with 8% experiencing high-impact chronic pain that limits daily activities.
  CDC

• In 2022, the U.S. recorded approximately 107,500 drug overdose deaths, with opioids involved in nearly 75% of these cases.
  CDC

Texas Pain and Opioid Epidemic Statistics:

• In 2020, Texas reported 4,172 drug overdose deaths, with opioids accounting for a significant portion.
  Wikipedia

• The state has implemented various initiatives to combat opioid misuse, including prescription monitoring programs and public health campaigns.

Most Common Types of Pain:

• Low Back Pain: A leading cause of disability worldwide, affecting individuals across all age groups.
  World Health Organization

• Neck Pain: Prevalent among adults, often resulting from poor posture, injury, or degenerative diseases.

• Osteoarthritis: A degenerative joint disease causing pain and stiffness, commonly in the knees, hips, and hands.

Endocannabinoid System (ECS):

• ECS = CB1 (CNS) and CB2 (immune system) receptors, endogenous ligands (AEA, 2-AG), and enzymes (NAPE-PLD, FAAH, MAGL).

• Pain signal ↑ → AEA/2-AG release ↑ → CB1 activation ↓ nociceptive transmission and CB2 activation ↓ cytokine-mediated inflammation.

Pharmacodynamics:

• THC binds CB1 (GPCR) → cAMP ↓ → neuronal excitability ↓.

• CBD inhibits FAAH → AEA breakdown ↓ → prolonged CB1 activation.

• CBD modulates TRPV1 and PPARγ → anti-inflammatory effects.

Pharmacokinetics:

• THC: Oral bioavailability 6–20%, Tmax = 2–4 hours, hepatic metabolism (CYP2C9, CYP3A4), t1/2 = 25–36 hours.

• CBD: Oral bioavailability 6–19%, Tmax = 2–6 hours, hepatic metabolism (CYP3A4, CYP2C19), t1/2 = 18–32 hours.

Clinical Studies:

• 2020 Pain Medicine study: THC/CBD combination ↓ pain severity, ↑ quality of life in chronic pain.

• 2021 The BMJ: Small improvements in chronic pain relief; moderate-to-low certainty evidence.

Neuropathic Pain:

• Pain signal ↑ → peripheral sensitization (voltage-gated sodium channel activity ↑). THC activation of CB1 ↓ neurotransmitter release (e.g., glutamate) → pain signaling ↓.

• CBD: TRPV1 activation → nociceptor sensitization ↓.

Opioid-Sparing Effects:

• THC/CBD adjunctive use with opioids → μ-opioid receptor desensitization ↓ → opioid requirement ↓.

• 2021 BMJ Open: Observational studies suggest opioid dose ↓ with cannabis; randomized controlled trial evidence limited.

Anti-inflammatory Pathways:

• Chronic pain → pro-inflammatory cytokines (TNF-α, IL-1β) ↑. CB2 activation ↓ cytokine release.

• CBD inhibition of NF-κB → inflammation ↓.

IV. Cannabis Formulations, Dosing, and Pharmacology (10 minutes)

Formulations:

• Products: Tinctures, capsules, edibles, inhalation, topicals.

• THC
  ratios tailored for pain (e.g., 1:1 for balanced effects, high-CBD for inflammatory conditions).

Dosing Guidelines:

• Start low, go slow: THC starting dose ~1–2.5 mg, titrated based on tolerance and efficacy.

• CBD: Initial dose ~10–20 mg/day, titrated upward.

Pharmacodynamics of Interactions:

• THC: Additive sedation with benzodiazepines, synergistic effects with opioids (respiratory depression risk).

• CBD: P450 enzyme inhibition (CYP3A4, CYP2C19) → ↑ levels of warfarin, clobazam, anti-epileptics.

Pharmacokinetics of Interactions:

• THC metabolized via CYP2C9, CYP3A4 → drug levels affected by inducers (e.g., rifampin ↓ THC) and inhibitors (e.g., ketoconazole ↑ THC).

• CBD ↑ clobazam active metabolite (N-desmethylclobazam) via CYP2C19 inhibition.

V. Safety and Adverse Effects (10 minutes)

Adverse Effects:

• THC: Common = dizziness, dry mouth, tachycardia; Rare = psychosis, cannabis hyperemesis syndrome.

• CBD: Common = diarrhea, fatigue; Rare = hepatotoxicity (dose-related, especially with anti-epileptic drugs).

Drug-Drug Interactions:

• THC + sedatives (e.g., benzodiazepines) → ↑ CNS depression.

• CBD + warfarin → ↑ INR (CYP2C19 inhibition).

• THC/CBD + SSRIs → ↑ serotonin syndrome risk (serotonergic modulation).

Patient Counseling on Safety:

• Avoid driving/operating machinery.

• Proper storage to prevent pediatric access.

VI. Role of the Pharmacist (10 minutes)

Counseling Responsibilities:

• Educate on delayed onset with oral cannabis (Tmax = 2–4 hours) to prevent overdose.

• Monitor for efficacy using patient-reported outcomes (pain scales, QoL assessments).

Managing Drug-Drug Interactions:

• Adjust doses of CYP450-metabolized drugs (e.g., antiepileptics, warfarin).

• Avoid polypharmacy with sedatives unless carefully monitored.

Collaboration with Providers:

• Work with prescribers to integrate cannabis into multimodal pain management strategies.

VII. Case Studies and Application (5 minutes)

Case 1: Chronic Neuropathic Pain

• Patient with diabetic neuropathy started on THC
  1:1 tincture at 2.5 mg BID. After 4 weeks: Pain scale ↓ by 50%, gabapentin dose ↓ by 25%.

Case 2: Opioid Dose Reduction

• Cancer pain patient on 30 mg morphine TID. Added THC (2 mg QHS) + CBD (10 mg BID). Morphine dose tapered by 50% in 6 weeks without pain escalation.

VIII. Conclusion and Key Takeaways (5 minutes)

Medical cannabis, through ECS modulation, reduces nociceptive signaling and inflammation. THC and CBD offer potential opioid-sparing effects but require careful monitoring of pharmacokinetics and drug-drug interactions. Pharmacists must balance evidence-based use with safety counseling, ensuring patient-centered care while mitigating risks. Continued research and regulatory evolution will enhance the integration of medical cannabis into pain management.

References:

• 2020 Pain Medicine: https://academic.oup.com

• 2021 The BMJ: https://www.bmj.com

• 2021 BMJ Open: https://bmjopen.bmj.com

• 2022 BMJ Open: https://bmjopen.bmj.com

• Pain Management Nursing: https://www.painmanagementnursing.org