Study Notes: Marijuana, Psychostimulants, and Hallucinogens – Chemical and Pharmacological Aspects

Marijuana

Introduction to Marijuana

• Marijuana is produced from the flower of Cannabis Sativa.

• Hemp is a variety of cannabis used for industrial purposes, such as the production of oil, fiber, and paper, and is not exclusively used for harvesting drugs.

Chemical Compounds in Marijuana

• The main psychoactive compound in marijuana is Δ9-tetrahydrocannabinol (THC).

• Other important cannabinoids include cannabidiol (CBD) and cannabinol (CBN).

Absorption, Distribution, and Metabolism

• THC is lipophilic and is absorbed by the lungs and distributed in blood plasma.

• Oral use leads to poor absorption due to first-pass metabolism in the liver and storage in adipose tissue.

• THC accumulates in fat, leading to a slow release and long detection window in the body.

• Metabolism of THC involves conversion to 11-OH-THC (active) and then to THC-COOH (inactive), which is excreted in urine.

Key Equations:

• Conversion: $\text{THC} \xrightarrow{\text{liver}} 11\text{-OH-THC} \xrightarrow{\text{liver}} \text{THC-COOH}$

Pharmacokinetics and Detection

• THC can be detected in blood, plasma, saliva, and hair.

• Detection window varies: blood/plasma (hours to days), urine (up to 30 days or more in chronic users).

Endocannabinoid System

• Two main receptors: CB1 (central nervous system) and CB2 (immune system, peripheral tissues).

• CB1 is primarily found in the brain (basal ganglia, hippocampus, cerebellum, cortex).

• CB2 is found in immune cells, adipose tissue, and peripheral organs.

• Endogenous ligands: Anandamide and 2-AG (2-arachidonoylglycerol).

Mechanism of Action

• THC acts as a partial agonist at CB1 and CB2 receptors.

• Activation of CB1 inhibits neurotransmitter release (e.g., GABA, glutamate) by inhibiting calcium influx and opening potassium channels in presynaptic neurons.

Pharmacological Effects

• Euphoria, altered perception, relaxation, increased appetite, impaired memory and coordination.

• Adverse effects: anxiety, paranoia, cognitive impairment, and in some cases, psychosis.

• Withdrawal symptoms: insomnia, irritability, anxiety, decreased appetite.

Medical and Clinical Aspects

• THC is used medically for pain, nausea, and appetite stimulation.

• CBD has low affinity for CB1/CB2, lacks psychoactive effects, and is used for epilepsy and other conditions.

• THC is a Schedule I drug in the US (federally illegal, high abuse potential).

Table: Comparison of THC and CBD

Property	THC	CBD
Psychoactivity	Yes	No
CB1/CB2 Affinity	High	Low
Medical Uses	Pain, nausea, appetite	Epilepsy, anxiety
Legal Status	Schedule I (US)	Varies

Psychostimulants

Cocaine

• Cocaine is a psychostimulant drug derived from the Erythroxylum coca plant.

• It is extracted from coca leaves and converted to cocaine hydrochloride (Cocaine·HCl).

• Variants include crack (smoked, with baking soda/ammonia) and free-base (smoked, with ether or alcohol).

Pharmacokinetics and Metabolism

• Peak effects are faster with smoked/intranasal use than oral.

• Metabolized to benzoylecgonine (measured in urine for drug tests).

Mechanism of Action

• Cocaine is a non-selective monoamine reuptake inhibitor (blocks DAT, NET, SERT), increasing dopamine, norepinephrine, and serotonin in synapses.

Pharmacological Effects

• Euphoria, increased energy, alertness, sympathomimetic effects (increased heart rate, blood pressure).

• Adverse effects: anxiety, paranoia, aggression, cardiovascular risks.

• Chronic use can lead to tolerance, dependence, and withdrawal symptoms (fatigue, depression, irritability).

Medical and Clinical Aspects

• No standardized treatment for cocaine addiction; options include receptor blockers, antidepressants, and behavioral therapy.

Table: Cocaine vs. Amphetamines

Property	Cocaine	Amphetamines
Mechanism	Reuptake inhibitor	Promotes release of monoamines
Duration	Short	Longer
Medical Use	Local anesthetic	ADHD, narcolepsy

Amphetamines

• Increase synaptic monoamines by promoting release and inhibiting reuptake.

• Used medically for ADHD and narcolepsy; abused for stimulant effects.

MDMA (Ecstasy)

• Acts primarily by increasing serotonin release; also affects dopamine and norepinephrine.

• Effects: euphoria, empathy, altered sensory perception.

• Risks: neurotoxicity, dehydration, hyperthermia.

Hallucinogens

Introduction

• Hallucinogens are a class of drugs that alter perception, mood, and cognitive processes.

• Common examples include LSD, psilocybin, and mescaline.

Additional info: These notes focus on the chemical and pharmacological properties of psychoactive substances, including their mechanisms of action, metabolism, and clinical effects. While not a traditional organic chemistry chapter, the content is relevant to the chemistry of natural products, drug metabolism, and the structure-activity relationships of bioactive molecules.