10.1. Marijuana/cannabinoids:: History and basic pharmacology History and basic pharmac

Cannabis contains many

cannabinoids (natural).

Cannabinoids are especially concentrated in the

sticky, yellow resin secreted at the flowering top of the female plant.

Cannabis contains >110

cannabinoids (many of which are psychoactive)

Δ9-tetrahydrocannabinol (Δ9-THC or "THC")

seems to be the most important psychoactive compound

Other cannabinoids:

Δ8-THC, cannabinol, cannabidiol (CBD).

Marijuana refers to

dried cannabis and contains a mixture of leaves, small stems, and flowering tops

THC content varies

strain (breeding) and growing conditions.

If prevent pollination and seeding in female plants,

THC content is increased (sinsemilla = "without seeds")

THC content in seized marijuana has increased over the decades

2010s: 8-12% typical

Hashish is a dried resin concentration consisting of trichomes;

the plant part with the highest THC content). 20-60% THC.

Hash oil is an

alcoholic extraction from hashish

Dab includes

other extractions from cannabis. Can be >90% THC

Smoking

20-30% of the THC can be absorbed

Vaporizing

(including "dabbing")

Eating

Low absorption of THC due to first-pass metabolism in stomach and liver (but metabolic products are even stronger)

History of cannabis use

- Cannabis sativa (hemp) is one of the earliest cultivated non-food plants

- Hemp is among the strongest natural fibers

Throughout 1800s,

marijuana was legal and widely available in the U.S.

By the 1930s, Anti-marijuana propaganda was created:

movies ("Reefer Madness") and books. Spread false info that marijuana was a social menace that would lead to violent crimes

In the 1960s-70s, attitudes toward marijuana became more

lenient and cannabis usebecame very popular among counterculture

What schedule is marijuana?

marijuana is a Schedule I.

Current cannabis use

Cannabis is currently the most popular U.S. illicit drug

When is cannabis typically first used?

adolescence

potential medical uses of marijuana

Treatment of glaucoma - to decrease intraocular pressure

Antiemetic - to reduce nausea and vomiting (cancer patients)

Appetite stimulant (AIDS patients)

Anticonvulsant - to reduce seizures

Analgesic - to reduce pain

Many U.S. states have legalized medical marijuana, and some have legalized recreational marijuana.

But, still illegal at the federal level (Schedule I)

Cannabidiol (CBD):

thought to have similar benefits as THC without strong psychoactive effects

Synthetic THC approved in U.S. for treatment of

nausea and anorexia in AIDS and cancer patients.

- neuropathic pain

CBD medication approved in U.S. for

severe childhood epilepsy

Cannabinoids are

highly lipid soluble

THC reaches the brain quickly after

inhalation then, distributes to fat stores (depot binding), causing rapid decrease in blood concentration.

THC is distributed to

fat stores in the body (depot binding)

Oral THC has

Slower effects

This results in a long half-life of 20-30 hours

20-30 hours

Drug tests can detect single use

>2 weeks later (even longer with frequent use)

Metabolism is

mostly in liver

11-hydroxy-THC

Active metabolic product after oral consumption of Δ9-THC (first-pass metabolism), more potent than Δ9-THC itself

11-nor-9-carboxy-THC

Inactive metabolite used in drug test

THC effects of low to moderate doses: (Behavior and mood)

Disinhibition, relaxation, drowsiness, floating sensation

Enhanced feeling of well being, euphoria

Impaired short-term memory (see graph)

Impaired time estimation and reaction time

THC effects of low to moderate doses: (physiological)

Increased hunger ("munchies") - very reliable effect

Decreased muscle strength, small tremor

Increased heart rate (pounding)

Increased blood flow (causes red eyes, good for glaucoma)

Effects vary with

dose, setting, past exposure, expectations

THC effects in high doses: (behavior and mood)

Increasingly disorganized thoughts, confusion

Paranoia, agitation

Anxiety (dependent on setting)

Synesthesias and pseudohallucinations

THC effects at high doses: physiological

pronounced motor impairment

Not lethal

even at very high doses

Withdrawal symptoms

peak for 1-2 weeks after chronic use in humans (and are opposite to acute effects of cannabis):

Irritability

Anxiety

Depressed mood

Sleep disturbances

Heightened aggression

Decreased appetite

Factors contributing to increased risk of addiction

Early onset of use (young age)

Daily use

Effects of repeated cannabis: Tolerance

Behavioral tolerance

Pharmacodynamic tolerance: After repeated use, desensitization and downregulation of CB1 receptors in the brain,

Effects of repeated cannabis: Other adverse effects while still using the drug?

Amotivational syndrome

Impaired attention and memory

Reproductive system impairments in males

Spice and K2 are herbs laced with

synthetic cannabinoids sold under several names

Spice and K2 are marketed as

"safe" legal alternatives to marijuana.But not safe or legal!

spice and K2 can cause

Intoxication, withdrawal, psychosis, and overdose death