Cannabis

Dr. Basrai
Cannabis

Epidemiology

  • Most commonly used illicit substance world-wide

Cannabis Family

  • The two main subspecies of the cannabis family are

    • Cannabis indica: Higher ratio of THC to CBD

    • Cannabis Sativa: Higher ratio of CBD to THC

  • Hemp Plants have high concentrations of CBD and negligible THC thus are legal in a number of US States.

  • THC concentration is greater than 10% is considered high potency

Cannabinoids

  • Molecules which share the 21-carbon strcutur e of THC

  • 3 main cannabinoids: plant based, endogenous, synthetic

  • Plant Based:

    • THC and CBD

    • Hydrophobic, lipophilic because of long aliphatic chains

  • Endogenous:

    • Anandamide and 2-arachidonoylglycerol

    • Key ligand for CB1 and CB2

  • Synthetic Cannabinoids:

    • Lab produced

    • K2 and Spice

    • Urine Drug Screens can’t detect most synethetic cannabinoids because doesn’t match THC exactly

      • Dronabinol can be detected on UDS

Pharmacology

  • THC:

    • Partial agonist at CB1 and CB2 (CB1>CB2)

    • Modulates beta-2-adrenergic receptors

    • Modulates mu- and delta-opioid receptors

    • Metabolizes CYP3A4.

    • Inhibits CYP2C9

    • Induces CYP1A2

    • Metabolized from THC to 11-hydroxy-THC which is psychoactive

    • 11-hydroxy-THC is metabolized into THC carboxylase which is not psychoactive.

    • Elimination half-life is 25-36 hours. Longer in habitual users

    • Eliminated mostly in feces followed by urine

  • CBD:

    • Low affinity to CB1 and CB2. No euphoric or intoxication effects

    • Modulates mu- and delta-opioid receptors

    • 5-HT1A partial agonism

    • Modulates the psychomimetic effects of THC

    • Potentially has antipsychotic, antianxiety anticonvulsant properties

    • Metabolized by CYP3A4

    • Inhibits CYP2D6 and CYP2C9

  • Synthetic Cannabinoids

    • Full agonist of CB1

    • Very High receptor affinity compared to THC

Endocannabinoid System

  • Two key receptors: CB1 and CB2

    • CB1:

      • Widely expressed in various brain regions

      • Highest concentration is the hippocampus and basal ganglia

      • Also expressed throughout the body in most tissues and organs in the periphery

    • CB2:

      • Primarily in the periphery

Toxicology Testing

  • UDS has immunoassays that test for the presence of delta-9-THC metabolites

  • False positives are rare but causes include

    • PPI

    • Hemp Seed oil

    • NSAIDS

    • Efavirenz

Dosing

  • THC potency:

    • Leaves and stems: 0.5%-5%

    • Hashish (dried cannabis resin with compressed flowers): 2%-8%

    • Sinsemilla (flowering tops of unpollinated female plants): 7%-14%

    • Hashish oil: 15%-50%

    • Butane has oil: 90%

  • 1 Joint typically has 0.6-1mg of THC

  • >12 g for women > 14g for men can cause delirium, postural hypotension, myoclonic jerking, and panic attacks

Time of Action

  • Smoking: onset 5 min, peak 30 min, duration 2-4 hours

  • Vaporization: onset 5 min, duration 2-4 hours

  • Mucosal: onset 14-30 min

  • Edibles: onset 1-3 hours. Duration 6-8 hours

Cannabis Intoxication

  • Adrenergic effect (Given CB-1 colocalizes with beta-2 adrenergic receptors):

    • Tachycardia

    • BP variability

    • Tachypnea

  • Cognitive effect

    • Short-term memory impairment

    • Judgement impairment

    • Concentration impairment

    • Motor impairment

    • Anxiety

    • Hypervigilance

    • Psychosis

  • Cannabis hyperemesis syndrome

    • Associated with heavy cannabis use

    • Report relief with hot showers

    • Treatment

      • Cessation of cannabis use

      • Oral dopamine antagonist

      • Capsaicin to the abdomen

Withdrawal

  • Symptoms non specific: Anxiety, sleep disturbances, irritabilitiy, restlessness

  • Onset within 24-72 hoiurs

  • Peak at 1 week

  • Resolves in 1-2 weeks

Treatment of Cannabis Use Disorder

  • Currently no US FDA approved medications

  • Medications that have been used off-label:

    • Agonists:

      • Drobanilol (50-120 mg/day)

        • Reduces withdrawal symptoms.

        • Studies failed to hshow that it reduces cannabis use.

        • Clinical trial of combination dronabinol and behavioral therapies did not sure benefit over placebo

      • Nabilone:

        • Recent human laborartory studies show that it is promising potential treatment of CUD as it decreases subjects choice to self-admnister cannabis in the lab setting.

    • Antagonist:

      • Rimonabant:

        • Initial studies showed recduction in subjective “high” of cannabis

        • Clinical research stopped because produced increased anxiety, depression, and suicidality

    • Non-Cannabinoid Pharmacologies:

      • Lofexidine: Centrally acting alpha-2 agonist

        • Reduces withdrawals

        • Combined with dronabinol has been studied which showed decreased withdrawal symptoms and cravings

    • Targeting GABA and Glutamate

      • Gabapentin (1200 mg/day):

        • Initial study had high drop out rate but did show decreased withdrawal asymptoms and reduced cannabis use compared to placebo

      • N-acytcysteine (1200mg bid):

        • NAC + CM showed reduction in cannabis consumption compared to CM alone

  • Psychosocial Interventions

    • Contingency management with cognitive behavioral therapy.

References

  1. Marienfeld, Carla, editor. Absolute Addiction Psychiatry Review: An Essential Board Exam Study Guide. Springer Nature, 2020.

  2. American Society of Addiction Medicine. "A Review of Potential Pharmacological Treatments for Cannabis Abuse." ASAM Blog, 9 Aug. 2021, https://www.asam.org/blog-details/article/2021/08/09/a-review-of-potential-pharmacological-treatments-for-cannabis-abuse.

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