Lecture 8 - Cannabis and THC

What is Cannabis?

  • Cannabis refers to both the drug marijuana and the plant species under the genus Cannabis.

  • Most widely known and cultivated species: Cannabis sativa.

  • Two pharmacologically active compounds:

    • Tetrahydrocannabinol (THC)

    • Cannabidiol (CBD)

Decarboxylation Process

  • Tetrahydrocannabinolic acid (THCa) and Cannabidiolic acid (CBDa) are not pharmacologically active.

  • They convert into THC and CBD through a process called decarboxylation.

  • Decarboxylation occurs when the plant is heated, burned, or dried, releasing carbon dioxide and producing the psychoactive components.

History of Cannabis

  • Used for thousands of years; originally by ancient Hindus in India and Nepal.

  • Historical usage in religious and cultural ceremonies.

  • Modern usage primarily for recreational purposes, with an emerging interest in clinical applications, although many claims lack substantial support.

Legal Status of Cannabis

  • Global Legal Status for Recreational Use:

    • Legal

    • Illegal but decriminalized

    • Illegal but often unenforced

    • Illegal

    • Legality unknown

  • Global Legal Status for Medical Use:

    • Legal for any adult use.

    • Legal for medical use.

    • Illegal or unknown status.

Legalization in Canada

  • Cannabis was illegal in many parts of the world; however, the federal Cannabis Act took effect on October 17, 2018.

  • Canada became the second country in the world to legalize:

    • Cultivation

    • Possession

    • Acquisition

    • Consumption of cannabis and its derivatives.

Historical Perception of Cannabis

  • 1920s - portrayed as an "evil" drug; laws were enacted banning its use.

  • 1930s - perceived as a narcotic.

  • 1940s - depicted as a "killer drug"; still considered illicit in several areas today.

Cannabis Regulation in Canada

  • From 2017, there were approximately 48,000 arrests related to cannabis, with 80% linked to possession.

  • Key goals of cannabis legislation in Canada:

    • Legalize and regulate the sale of recreational cannabis.

    • Restrict cannabis access to youth.

    • Limit the illicit cannabis trade.

  • Controlled Access for Adults (18+):

    • Individuals can possess up to 30 grams of legal cannabis.

    • Share up to 30 grams with other adults.

    • Purchase cannabis products from provincial retailers or online.

    • Grow up to 4 cannabis plants from licensed seeds.

    • Make cannabis products at home (e.g., edibles).

Cannabis Use Statistics in Canada (2021-2022)

  • Data adapted from the Health Canada Survey 2022 reveals trends in cannabis use, product preferences, and effects of cannabis among users in the past year.

  • Effects of cannabis use: Among frequent users, various insights and statistics were shared but omitted here.

Cannabis Varieties and Potency

  • Terminology and Potency Levels:

    • Hashish: Dried portions of the female flower (high potency; 10-20%)

    • Ganja: Dried tops of the female flower (medium potency; 5-8%)

    • Marijuana: Dried remainder of the plant (low potency; 2-5%)

  • Growers have increasingly bred cannabis to increase THC concentrations while reducing CBD.

  • Street Names for Cannabis: Numerous names include:

    • Airplane, Astro turf, Aunt Mary, Black Bart, Bud, Ganja, Weed, etc.

Routes of Administration

  • Methods to consume cannabis include:

    • Cigarettes ("joints"): Dried marijuana buds mixed with tobacco.

    • Cigars ("blunts"): Sliced open and filled with marijuana.

    • Vaping: Hash oil or marijuana in an electronic device.

    • Pipes: Higher levels of drug throughput compared to other methods.

    • Bongs: Water pipes that increase THC concentration.

    • Edibles: Includes gummies, baked goods, and teas infused with cannabis.

THC Mechanism of Action

  • THC was first isolated and is known for its psychoactive properties. Its chemical structure is complex, linked to specific receptors in the human body.

  • Cannabinoid Receptors:

    • Discovered CB1 and CB2 receptors in the 1990s.

    • CB1 receptors primarily found in the brain and influence various functions like motor activity, appetite, pain perception, and short-term memory.

    • CB2 receptors are found largely in the immune system and other body parts, influencing gut health, kidney functions, and the cardiovascular system.

THC Pharmacokinetics

  • Administration via a joint:

    • Typically contains 75 mg of THC; approximately 25 mg is found in the smoke, and 5-10 mg is absorbed into the bloodstream.

  • Oral ingestion (e.g., dronabinol or edibles):

    • yields 10-20% of the dose into the bloodstream due to first-pass metabolism, creating a longer-lasting active metabolite, 11-hydroxy-delta-9-THC.

  • Effects and Duration: The "high" occurs quickly (varies by method) and lasts approximately 2-3 hours. THC easily crosses both the blood-brain barrier and the placental barrier. The inactive metabolite, carboxy-THC, has a half-life of 30-60 hours, making it a useful biomarker.

Pharmacological Effects of THC

  • Notable effects include:

    • Analgesic properties

    • Decreases body temperature

    • Alters mood (calming effect)

    • Distorts temporal perception and induces memory impairments

    • Increases appetite and weight gain

    • Potentially causes bronchial irritation/inflammation

THC Tolerance and Dependence

  • Mechanisms include:

    • Down-regulation of cannabinoid receptors

    • Receptor internalization (less significant)

  • Symptoms of withdrawal syndrome can include:

    • Depressed mood

    • Insomnia

    • Loss of appetite

    • Irritability

Therapeutic Applications of Cannabinoids

  • Consideration of both THC and CBD is crucial when discussing therapeutic applications of cannabis.

  • Commonly self-prescribed for conditions including:

    • Chronic pain (e.g., back pain)

    • Sleep disorders

    • Anxiety and depression

    • Muscle spasticity associated with multiple sclerosis.

  • Nabiximols (Sativex):

    • Contains THC and CBD (1:1 mixture).

    • Administered in a mouth spray, approved in several countries for relief of muscle spasms and other symptoms associated with MS.

  • Dronabinol (Marinol):

    • Used as an appetite stimulant for AIDS patients and anti-nauseant in chemotherapy.

    • Can lower intra-ocular pressure, potential avenues remain largely under-studied.

Anandamide

  • Anandamide serves as an endogenous cannabinoid in the body, binding to the same receptors as THC, but functioning as a weaker agonist, activating approximately 50% of available receptors while THC activates around 20%.

Cannabinoid Receptors

  • Broadly distributed throughout the entire body:

    • CB1 Receptors: Found in areas that modulate movement, perception, and memory.

    • CB2 Receptors: Found in areas affecting gut, immune functions, and various organ systems.

Cannabinoid Antagonists

  • Provide a dose-dependent blockade against marijuana intoxication and may enhance memory and learning.

  • Rimonabant (Acomplia): Withdrawn globally due to severe psychiatric side effects.

Conclusion

  • Content culminates in bridging understanding of THC and cannabis, potential therapeutic applications, historical contexts, and the evolving legal landscape around this compound.