Pharmacology of Cannabis and Cannabinoids Notes

Intended Learning Outcomes (ILOs)

  • Understand the history of cannabis use and its current recreational use.
  • Recognize specific cannabinoid receptors and their locations.
  • Comprehend the endocannabinoid system and its potential functions.
  • Appreciate the central nervous system (CNS) and peripheral effects of cannabinoid receptor activation.
  • Identify the main behavioral and physiological effects of cannabis and cannabinoid receptor-activating agents.

Introduction to Cannabis

  • Source: Cannabis is produced from the plant Cannabis Sativa (hemp).
  • Uses: Historically used for rope, cloth, and paper; seeds provide oil and birdfeed.
  • Psychoactive Component: Δ9 Tetrahydrocannabinol (THC), concentrated in the sticky resin of female plants.

Historical Context of Cannabis Use

  • Ancient Use: Over 4000 years ago in China, India, and the Middle East for treating malaria, pain, constipation, and rheumatism; famously used by Queen Victoria for menstrual pain.
  • Legal History: Outlawed in the UK in 1928; however, recreational use remains prevalent.

Non-Medicinal Use of Cannabis

  • Cultural Significance: Used in religious rituals, referred to as "ganjika" in Sanskrit.
  • Literary References: Mentioned in works like Shakespeare's sonnets.

Modern Legal Context

  • Current Status: Legalization/decriminalization varies; illegal to possess or distribute in the UK without a license.
  • Punishment: A cannabis warning issued for possession of less than 1 ounce for personal use.

Constituents of Cannabis

  • Compounds: Over 480 compounds discovered, including over 60 cannabinoids (C21 terpenophenolic compounds), primarily phytocannabinoids.
  • Major Cannabinoids: Cannabidiols (most abundant) and THC (primary psychotropic compound).
  • Variation Factors: Composition can vary significantly based on preparation and growth conditions.

Smoking and Absorption of Cannabis

  • Usage Amount: A typical joint contains 0.5 - 1g of cannabis with THC concentration around 4%, yielding approximately 40mg of THC per joint.
  • Delivery Comparison: Sativex dosage is about 31.6mg THC with 8 sprays a day.
  • Absorption Efficiency: Approximately 20% of THC is absorbed during smoking; precision of inhalation affects absorption levels.

Metabolism of Cannabis

  • Oral Absorption: Poor oral absorption leads to low plasma levels due to degradation and first-pass metabolism.
  • Elimination Half-Life: Blood THC levels drop quickly post-smoking, but metabolites linger in fat tissues, detectable for up to two weeks after single use.

Cannabinoid Receptors: CB1

  • Discovery: Identified in 1988; implicated in areas related to behavioral effects.
  • Key Agents: THC and endocannabinoids (AEA, 2-AG) are agonists; SR141716 (Rimonabant) is an antagonist.

Cannabinoid Receptors: CB2

  • Discovery: Identified in 1993, found on immune cells and peripheral tissues.
  • Functional Properties: Agonist 2-AG; relevant in pain and inflammation therapies.

Mechanisms of CB1 Activation

  • Mechanism: CB1 receptors inhibit adenylyl cyclase (AC) activity via Gi/Goα subunits, leading to a reduction in intracellular cAMP levels.
  • Effect on Calcium Channels: G-proteins can influence calcium channels, which are vital for neurotransmitter release.

Effects of Cannabinoid Activation

  • Cognitive Impairment: Cannabinoids impair cognitive functions such as memory, demonstrated through various studies, including microinjections in models.
  • Reward Pathway: Evidence shows that cannabinoids are linked to reward responses, as demonstrated in monkey studies measuring behavioral changes in response to THC.

Stress, Mood, and Mental Health

  • Psychiatric Concerns: Correlation exists between cannabis use and mental health degradation. The relationship remains ambiguous whether cannabis is a causal factor.
  • Neuropsychiatric Studies: Research indicates the mental health impact varies significantly based on the frequency and intensity of use.

Pharmacological Applications

  • Pain Management: Cannabinoids have shown potential in alleviating neuropathic pain and nausea associated with severe pain treatments.
  • Appetite Regulation: Cannabinoids stimulate appetite through specific receptor pathways, impacting conditions such as cachexia.

Future Prospects of Cannabinoids

  • Therapeutic Potential: Observations indicate cannabinoids could act as neuroprotectants and anti-inflammatory agents, necessitating further study and future application strategies.