Cannabis

cannabis oral administration

slow absorption, long duration

not ionised, extremely lipid soluble

onset 30-90 min post ingestion

first pass metabolism

1/3 potency of inhalation

cannabis inhalation administration

rapid absorption, peak blood levels <10min, peak effects around 30 min, depth and frequency of inhalation alters absorption

distribution of cannabis

reaches all bodily areas but focused in lungs, kidney, liver, crosses BBB and placental barrier, 1% enters brain

excretion of cannabis

initial metabolism in lungs or GI tract, most in liver - break down into many metabolites 

Phase 1 excretion - redistribution effect - half-life 30-80 min 

Phase 2 excretion - metabolism effect - half-life 20-30 hours

traces remain 1-4 weeks after

CBD half-life: 9-32 hours

2 types of cannabinoid receptors

CB1 (CNS, brain stem) and CB2 (outside CNS, spleen, immune system)

Endogenous ligands

naturally occurring molecule in body which binds to and activates a specific receptor

endocannabinoid system includes

CB1 and Cb2 receptors, endogenous ligands

endocannabinoids alter the functioning of

GABA, NE, DA, 5-HT, histamines, glutamate, opioid peptides

endocannabinoids increase the synthesis of

NE, DA, 5-HT, GABA

endocannabinoids alter receptors for

NE, Ach, DA

Endocannabinoids potentiate the action of

NE, Ach, Da

Reinforcing effects of cannabis

receptors in mesolimbic DA pathway inhibit GABA = more dopamine

also interacts with opioid receptors

cannabis effects on body

time distortion, disrupts memory, choice RT and complex tasks most impaired

Conditioning in animals

mice: cannabinoid tetrad: less SMA, muscle rigidity, pain sensitivity and hypothermia

SMA biphasic effect: increase then decrease 

ataxia at high doses 

interferes with STM

animals self administer

discrimination in animals 

reliably discriminate form placebo, partial generalisation to sedatives, no generalisation to CBD

tolerance in animals

develops fast (5-6 days) to most effects, increased SMA, slower development for decreasing SMA

no tolerance for anorexic effects

withdrawal in animals

mild, masked by long half life

discrimination in humans

state dependent learning (disassociation), can discriminate

self administration in humans

stable intake, more reinforcing with higher THC content

tolerance in humans

more tolerance with higher doses/more frequent use

Withdrawal in humans

starts 1-3 days post abstinence, peaks at 2-6 days, lasts 2 weeks, mild

negative effects of cannabis

respiratory disease, loss of mental functioning (altered hippocampus), amotivational syndrome, less reward response in nucleus accumbens