Drugs, Brain and Behaviour (13) - Marijuana & Cannabinoids

Cannabis

A psychoactive drug derived from dried flowering tops, leaves, and stems of female plants in the Cannabis genus. Two types:

• Cannabis sativa

• Cannabis indica

Part of the plant with the Highest THC Concentration

Flowering tops (“buds”)

Cannabinoids

Chemical compounds in cannabis that affect the brain and body (e.g. THC & CBD)

THC (Δ9-tetrahydrocannabinol)

Primary psychoactive compound producing the “high”. Preventing pollination increases THC production in female plants.

CBD (cannabidiol)

Non-intoxicating cannabinoid that may reduce anxiety and counteract THC effects.

How is Cannabis potency increased?

Due to selective breeding and improved cultivation methods.

Risks of THC

• Dependence

• Psychosis risk

Other Forms of Cannabis

Hashish - Concentrated Cannabis made from resin/kief of plant trichomes.

Hash oil - Highly concentrated Cannabis extract made using solvents (Very high THC content).

Most common administration route of Cannabis

Smoking Cannabis absorbs: ~20–40% of THC (e.g Joints, pipes, and bong). But exposure to toxic combustion products.

Vaporising

Heating Cannabis to release Cannabinoids without burning → Produces fewer toxins than smoking.

Oral Administration

Slower onset but stronger and longer-lasting effects (e.g. through edibles)

History of Cannabis use

• Used for thousands of years for medicine and rituals in China, India, and the Middle East.

• 19th Century: Popular among European intellectuals.

• 20th Century: Increased via migration and counterculture movements.

Legal status of Cannabis

Varies globally with decriminalisation and legalisation in some regions. (e.g. Regulated sales in coffee shops in Netherlands).

Medical uses of Cannabis

• Glaucoma - Cannabis reduces intraocular pressure.

• Nausea reduction

• Appetite stimulation - Useful in AIDS and cancer patients

• Pain Relief

• MS treatment -Sativex reduces muscle spasticity.

CB1 receptor

Main cannabinoid receptor responsible for psychoactive effects. Found primarily in the brain (basal ganglia, hippocampus, cerebellum).

CB1 Density in Brainstem

Low → low risk of fatal respiratory depression.

CB2 receptor

Found mainly in immune and glial cells. Regulates immune responses.

Cannabinoid receptor type

G-protein-coupled receptors linked to Gi proteins.

Effect of receptor activation

Reduces neuronal excitability and neurotransmitter release.

THC absorption

Rapid after inhalation due to lipid solubility.

THC distribution

Accumulates in fat tissue.

Effect of fat storage

Prolonged release and long detection times.

THC metabolism

Occurs in the liver.

Active THC metabolite

11-hydroxy-THC.

Inactive metabolite

11-nor-9-carboxy-THC.

THC excretion

Via feces and urine.

Drug detection

THC can be detected weeks after use.

Low-dose cannabis effects

Mild sensory changes and lightheadedness.

Moderate-dose effects

Euphoria, relaxation, and sociability.

High-dose effects

Altered perception, time distortion, and floating sensations.

Physiological effects

Increased heart rate, red eyes, and increased appetite.

“Munchies”

Increased appetite after cannabis use.

Adverse psychological effects

Anxiety, paranoia, and depersonalisation.

Cognitive impairment

Reduced memory, attention, and decision-making.

Memory effect of THC

Impairs explicit memory recall.

Cannabis and dopamine

THC increases dopamine in nucleus accumbens.

Conditioned place preference (CPP)

Low THC doses can produce reward-based preference.

High-dose THC effect

Can produce aversion instead of reward.

Self-administration findings

Monkeys self-administer THC; rats show mixed results.

Synthetic cannabinoids

Lab-made compounds that activate cannabinoid receptors.

Example synthetic cannabinoid

WIN 55,212-2.

Difference from THC

Often full agonists, producing stronger effects.

Risks of synthetic cannabinoids

More severe and unpredictable side effects.

Cannabinoid antagonist

Drug that blocks cannabinoid receptors.

Example antagonist

Rimonabant.

Effect of Rimonabant

Reduces cannabis effects and drug self-administration.

Endocannabinoid system

Body’s natural cannabinoid signalling system.

Endocannabinoids

Naturally produced cannabinoid-like molecules.

Examples of endocannabinoids

Anandamide and 2-AG.

Endocannabinoid synthesis

Produced on demand rather than stored.

Retrograde signalling

Endocannabinoids travel from postsynaptic to presynaptic neuron.

Effect of retrograde signalling

Reduces neurotransmitter release.

Functions of endocannabinoids

Regulate appetite, reward, stress, and social behaviour.

Cannabis and appetite

Activation increases feeding and food pleasure.

Tolerance to cannabis

Reduced effects with repeated use.

Tolerance develops to

Analgesic and motor effects.

Mechanism of tolerance

Reduced CB1 receptor function

Long-term cannabis effects

Impair executive functions.

Affected cognitive domains

Memory, attention, decision-making, impulse control.

Persistence of effects

Some impairments remain after abstinence.

Cannabis dependence

Compulsive use with withdrawal symptoms.

Withdrawal symptoms

Irritability, anxiety, reduced appetite, aggression.

Risk of dependence

~9–10% overall; up to 50% in daily users.

Cannabis and psychosis

Associated with increased risk, especially in vulnerable individuals.

Psychosis relationship

Cannabis may trigger or worsen symptoms.

Causation issue

Difficult to separate cannabis effects from genetic/environmental factors.

Core mechanism of cannabis

Acts via CB1 receptors affecting neurotransmission and dopamine.

Core behavioural effects

Euphoria, altered perception, and relaxation.

Core risks

Cognitive impairment, dependence, and psychosis.