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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
  • cannabis users appear to have ~25% higher blood levels of lead and cadmium as the cannabis plant is known to be a scavenger of heavy metals

cannabis use disorder

  • 10-30% who use marijuana will develop marijuana use disorder, meaning that they are unable to stop using marijuana even though it’s causing health and social problems in their lives.1)
  • a large genomic study found 22 loci relevant to Europeans, two each among Africans and East Asians, and one in people with mixed ancestries which were associated with risk of developing cannabis use disorder 2)

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 3)
  • 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.4)
  • 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 areas5)

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;
  • increases unprotected sexual activity resulting in increased births (despite its reduction in fertility) and increased STIs
    • increases attention to the immediate hedonic effects of sexual contact
    • impairs judgement or limits communication between partners
    • less attention to consideration of long-term consequences of their behavior
  • Effective antiemetic in chemotherapy? - hence synthetic drugs nabilone/dronabinol;
  • Reduces intraocular pressure → use in open angle glaucoma;
  • THC → bronchodilator but usually bronchoconstricts 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: 2023/11/26 04:14 by gary1

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