PSY 134 - nicotine and cannabinoids

cannabinoids

molecules with c-21 structure, activate cannabinoid receptors, includes endogenous molecules

sinsemilla

cultivation technique to increase resin and THC production in female plants by isolating them from male plants (without seeds)

3 psychotropic phytocannabinoids in cannabis

delta-9-THC (also derived from decarboxylation of cannabinoid acids in cannabis), delta-8-THC, propyl homologue of delta-9-THC

neuropharmacological mechanism of cannabinoids

Gi/o-coupled receptors

nicotinic receptors: beta-2

confers high binding affinity

nicotinic receptors: alpha-4-beta-2

mesolimbic DA; target of Chantix

nicotinic receptor stimulation

rapid desensitization, complete inactivation, rebound hyperactivity

route determines drug effects (both nic and THC)

nic (tobacco/oral snuff > gum/cigs); THC (eddies: longer time course w less potency)

Pharmacokinetics of nicotine

passively absorbed, can be detected by cotinine in urine, metabolized by P450 enzymes in liver, half life 2 hours (half life cotinine 19 hours)

Pharmacokinetics of THC

lipophilic (accumulates in fat and less vascular tissue), metabolized by P450 enzymes in liver, half life 20-60 hours (detectable for up to 27 days for chronic users)

cigarette dependence/addiction

first cig earlier in day, more when awoken at night, more craving, more difficulty restraining, more when ill

marijuana smoking dependence/addiction

type one (multiple times/day, perceives problem, voluntary tx referral, moderate WD); type two (every couple days, involuntary tx referral, mild WD); *NOTE: high relapse rates for both

withdrawal in animals

IV nic (teeth chattering, gasps, ptosis/drooping eyelid), IP THC (wet dog shakes, facial rubbing), nic mini-pump (inc ICSS thresholds, inc somatic sxs up to 48 hrs)

substitution/replacement therapy

gradually decreasing dose of abused substance

partial agonist therapy

e.g. Chantix (varenicline), PO (slower pharmacokinetics), also acts as competitor to full agonist

indirect DA agonist/antidepressant therapy

e.g. Zyban (buproprion), pre-increase DA so the increase is not detectable when drug is taken

augmenting endocannabinoid signaling

FAAH (fatty acid amide hydrolase) normally breaks down endocannabinoids; inhibit FAAH, keeps CB1 receptor stimulated; regional positive feedback loop (bc endocannabinoid production is activity-dependent); increased endocannabinoid activity increases retrograde inhibition of presynaptic neuron