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marijuana

marijuana / cannabis / THC

introduction:

  • Recreational smoking of the products of the subtropical plant Cannabis sativa, mainly its dried resin (hashish - smoked in a pipe), oily extract from flowering tops (hash oil) , or the chopped flowering tops of the female plant (marijuana “grass” - smoked as cigarette) has become popular in Western cultures since 1960.

potential acute medical complications for THC use

other longer term effects

  • impaired short term memory
  • impaired motor coordination
  • altered brain development
  • poor education outcomes
  • 6x risk of triggering schizophrenia compared to non-smokers
    • deposits 3 times more tar in the lungs than cigarette smoking
  • carcinogenic - perhaps for head and neck, lung, testicular
  • use in pregnancy - see risks below, eg. 10x risk leukaemia

chemical constituents:

  • Some 60 cannabinoids, with delta9-tetrahydrocannabinol (THC) - the main intoxicating material which makes up 1-6% total weight of marijuana, 6-10% of hashish, & 30-60% of hash oil!!
  • In addition, there are 8 other classes of compounds including 421 compounds that are xenobiotic - that is substances foreign to th body not used for food or fuel & include alkaloid derivatives of: spermidine, sterols, terpenes, flavanoid glucosides;
  • Under heat, cannabinoids rapidly decarboxylate, & at 200-400° C aromatisation occurs;
  • At least 150 polycyclic aromatic hydrocarbons have been identified in marijuana smoke, & the proportion of high MW compounds, particularly the carcinogen benzo[a]pyrene, are greater than in tobacco smoke;
  • Other constituents of marijuana smoke include phenols, phytosterols, acids & terpenes, otherwise similar to tobacco smoke with equivalent concentrations of CO, HCN, nitrosamines, & similar “tar yield”;

P/K of the cannabinoids:

  • Biovailability of THC is 20% when inhaled & 6% when ingested;
  • As they are very fat soluble, have a T½ = 8days , thus 1 dose of THC takes 1 month to be eliminated as it is stored in liver, spleen & fat, although < 1% reaches brain, testis;
  • THC is a polar compound which is slowly metabolised into at least 80 water soluble, non-psychoactive metabolites which are excreted via liver/GIT (80%) & urine (20%);
  • THC crosses placenta & transferred into breast milk;

effects of cannabinoids:

  • The two main constituents of cannabis, cannabidiol and Δ(9)-tetrahydrocannabinol (THC), have opposing effects both pharmacologically and behaviourally when administered in the laboratory
  • A THC receptor has been identified & cloned in rat brain, & there is evidence that it may modulate dopaminergic, GABA-ergic, serotoninergic & cholinergic activity, thus suggesting the existence of multiple receptor subtypes.
  • THC appears to act on CB1 receptors on AMPA-producing astrocytes in rats, the resulting AMPA then modulates surrounding neuronal synapses involved in short term memory 1)
  • the antagonistic effects of cannabidiol at the CB(1) receptor are probably responsible for its profile in smoked cannabis, attenuating the memory-impairing effects of THC.2)
  • α-7-nicotinic acetylcholine receptors (α7nAChRs) modulate effects of Δ9-tetrahydrocannabinol (THC)
  • kynurenic acid (KYNA) is an endogenous negative allosteric modulator of α7nAChRs.
    • research drug Ro 61-8048, is a kynurenine 3-monooxygenase (KMO) inhibitor and has been shown to increase brain KYNA levels and attenuate cannabinoid-induced increases in extracellular dopamine in reward-related brain areas3)

immediate:

psychoactive:

  • pleasant dreamy state, drowsiness, anxiolytic, analgesic impaired attention/cognitive/psychomotor performance which may persist for >6wks, even after 1 dose esp. short-term memory impairment & thus impaired learning;
  • Effective antiemetic in chemotherapy? - hence synthetic drugs nabilone/dronabinol;
  • Reduces intraocular pressure → use in open angle glaucoma;
  • THC → bronchodil. but usually bronchoconst. if inhaled as other agents in smoke?;
  • Effective in pediatric refractory epilepsy as anticonvulsant;

other:

  • Cannabis extracts are mutagenic in standard in-vitro & in-vivo tests;
  • Cannabinoids also:
    • impair DNA & RNA synthesis in cell cultures;
    • inhibit primary immune response & resistance to HSV in rats;
    • Daily use → high risk of head & neck cancers within 5-20yrs (average approx.10yrs)
      • → ? responsible for 70% H&N cancers under age 40yrs in US;
      • → risk of lung cancer within 10-15yrs;
    • May trigger schizophrenia - 6 x risk if use on > 50 occasions cf non-users;

Use in pregnancy or immediately prior to pregnancy :

  • → 10 x risk of leukaemia in child;
  • → lower birth weight, lower head circumference, high-pitched cries;
  • → decr. development & behaviour change (all animal species studied);
marijuana.txt · Last modified: 2019/10/09 08:17 by wh