marijuana / cannabis / THC

see also:

• Addiction medicine - drug and alcohol - main index and links
• drug dependency
• cannabinoid hyperemesis
• Wikipedia - marijuana
• NSW Govt - facts and links on marijuana

• 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”/“weed” - smoked as cigarette or inhaled via bongs) has become popular in Western cultures since 1960.
• cannabigerol is a precursor of many other phytocannabinoids, including delta-9-tetrahydrocannabinol (THC), cannabidiol, and cannabichromene
• smoking or vaporising cannabis produces a rapid and transient peak in blood and oral fluid THC concentrations. When taken orally, cannabis is absorbed more slowly through the gastrointestinal tract, producing far lower blood THC concentrations.

• native to warmer parts of the world, being Eastern Asia and Central and South America
• less dense in form and characterised by tall, slender structures with narrow leaves
• sativa is a subspecies of the cannabis plant known for its distinct characteristics and effects and are typically associated with energising and uplifting properties
• medicinal “sativa” is usually dispensed as dried flowers and in Australia requires a TGA approved vaporizer (although many use bongs) and a small weighing scale
  • prescriptions are usually 30g and “dose” is 0.1g and patients can be prescribed up to 60g per month at a cost of ~$285/month

• native to Afghanistan, India, Pakistan and Turkey
• have a compact, bushy appearance, indica plants typically have broader leaves and a shorter structure
• Indica strains often contain varying ratios of cannabinoids and terpenes, contributing to a diverse array of aromas and flavours. Indica strains are typically associated with relaxation and sedation.

• Hybrid strain options combine equal amounts of sativa and indica strains, that are anecdotally described as having a balance effect of both subspecies Sativa and Indica
• the process of hybridisation has led to the thousands of cannabis varieties globally and means there are now limited pure Sativa or Indica strains.

• see https://www.tga.gov.au/medicinal-cannabis-guidance-documents
• made legal in Australia in 2016
• different medicinal cannabis products are available to treat different conditions but are highly regulated and requires prescription from an authorized prescriber
• most medicinal cannabis products have not been assessed for safety and efficacy by the TGA and are not registered on the ARTG hence are “unapproved medications” requiring approvals for prescribing
  • as of 2024, only two products are registered on the ARTG:
    • Nabiximols (Sativex®), a schedule 8 controlled drug approved for the treatment of spasticity due to multiple sclerosis.
    • Epidyolex (Cannabidiol), a Schedule 4 prescription only medicine approved as an adjunctive therapy of seizures associated with Lennox-Gastaut or Dravet syndrome for patients 2 years of age and older.
• in Victoria, for nurse and medical practitioners seeking to prescribe a medicinal cannabis product not included in the Australian Register of Therapeutic Goods (ARTG), approval from the Commonwealth Therapeutic Goods Administration (TGA) is required. This approval can be obtained through either the TGA's Special Access Scheme , or by becoming an Authorised Prescriber. In addition, prescribers are required to apply for and hold a Victorian Schedule 8 treatment permit when prescribing a Schedule 8 medicinal cannabis product to a patient with a history of drug-dependence and prescribers and pharmacists are also required to check SafeScript prior to prescribing and dispensing Schedule 8 medicinal cannabis products to any patient. ⁴⁾
• most medicinal cannabis products contain the cannabinoids cannabidiol (CBD) and tetrahydrocannabinol (THC) and apart from 98% pure cannabidiol which is a schedule 4 medication, the remainder are schedule 8 medications
• none are subsidised by the PBS
• if you are travelling to Australia, you are able to carry up to a 3 months’ supply of medicinal cannabis for yourself or a passenger in your care, provided you have the relevant prescription from a medical practitioner.

• epilepsy in children and young adults ⁵⁾
• chronic non-cancer pain ⁶⁾
• multiple sclerosis ⁷⁾
• nausea and vomiting ⁸⁾
• palliative care ⁹⁾
• others as deemed appropriate by the medical practitioner

• Schedule 4 Prescription Only medicines
• cannabidiol comprises 98% or more of the total cannabinoid content of the medicine
• no other active ingredients
• forms available:
  • capsule
  • cream
  • dried herb
  • pressurised inhalation
  • oral liquid (mostly 100mg/mL but can range from 10mg/ml to 250mg/mL)
  • pastille
  • dermal patch
  • powder
  • tablet
  • topical liquid

• Schedule 8 Prescription Only medicines
• cannabidiol derived from cannabis comprises 60% or more and less than 98% of the total cannabinoid content of the medicine
• no other active ingredients
• forms available:
  • capsule
  • dried herb
  • oral liquid

• Schedule 8 Prescription Only medicines
• cannabidiol derived from cannabis comprises 40% or more and less than 60% of the total cannabinoid content of the medicine
• no other active ingredients
• forms available:
  • capsule
  • dried herb
  • inhalation
  • oral liquid
  • pastille

• Schedule 8 Prescription Only medicines
• other cannabinoids (including tetrahydrocannabinol) derived from cannabis comprise 60% or more and 98% or less of the total cannabinoid content of the medicine
• cannabidiol derived from cannabis comprises 2% or more and less than 40% of the total cannabinoid content of the medicine
• no other active ingredients
• forms available:
  • dried herb
  • inhalation
  • oral liquid

• Schedule 8 Prescription Only medicines
• other cannabinoids (including tetrahydrocannabinol) derived from cannabis comprise 98% or more of the total cannabinoid content of the medicine
• cannabidiol derived from cannabis comprises up to 2% of the total cannabinoid content of the medicine
• no other active ingredients
• forms available:
  • extract
  • dried herb
  • inhalation
  • oral liquid
  • pastille

• cannabinoid hyperemesis
• 5x risk of acute myocardial infarction (AMI/STEMI/NSTEMI) within 1hr of use compared with non-smokers (although risk is not as high as with cocaine use which gives 24x risk)
• pneumothorax or pneumomediastinum with with deep inhalation of marijuana involving breath holding or valsalva maneuvers
• paranoia / psychosis
  • 2022: 23 yr old cuts off his penis with scissors during a psychotic episode re-starting cannabis use
• e-cigarette or vaping pulmonary injury

• impaired fertility in women
  • a small 2025 study suggests that women exposed to THC appear to produce fewer embryos with the correct number of chromosomes but this needs further study
• epigenetic changes which could be passed to offspring
  • 2025 study finds numerous DNA methylation markers in the 15-year use blood samples, 22 that were associated with recent use, and 31 associated with cumulative cannabis use¹⁰⁾
    • multiple epigenetic changes associated with cannabis use had previously been linked to things like cellular proliferation, hormone signaling, infections, neurological disorders like schizophrenia and bipolar disorder, and substance use disorders.
• impaired short term memory
• impaired motor coordination
• altered brain development
• poor education outcomes
• 6x risk of triggering schizophrenia compared to non-smokers
• asthma
  • inhaling marijuana every day is associated with a 44% increased chance of developing asthma ¹¹⁾
• chronic obstructive pulmonary disease (COPD)
  • deposits 3 times more tar in the lungs than cigarette smoking
  • inhaling marijuana every day is associated with at least a 27% increased chance of developing COPD ¹²⁾
• carcinogenic - perhaps for head and neck, lung, testicular
  • adults with cannabis dependence, known as cannabis use disorder, are 3.5 to 5 times more likely to develop head and neck cancer than those who do not use the substance ¹³⁾
  • individuals with cannabis use disorder (CUD) are more than three times more likely to develop oral cancer within five years compared to those without CUD ¹⁴⁾
• 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
• heavy use of cannabis may increase gender specific risks, especially in those who also smoke tobacco: ¹⁵⁾
  • among female tobacco users, heavy cannabis use significantly increased risks for all-cause mortality (HR 2.25), CVD mortality (HR 2.56), and cancer mortality (HR 3.52)
  • male tobacco users saw an increased risk only for cancer mortality (HR 2.44)
  • overall, in the combined data for tobacco smokers and non-smokers:
    • heavy use of cannabis in females was associated with a higher risk of mortality from CVD (HR 2.67) and a non-significant increase in all-cause and cancer mortality after full adjustment
    • heavy cannabis use in males was associated with an increased risk of all-cause mortality, with a hazard ratio (HR) of 1.28, but not significantly with CVD or cancer mortality after adjusting for all factors.

• 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.¹⁶⁾
• 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 ¹⁷⁾
• another genomic study in 2025 found that lifetime cannabis use was associated with two genes¹⁸⁾
  • Cell Adhesion Molecule 2 (CADM2), a gene involved in cell assembly and in signaling between nerve cells, particularly in the brain - a gene linked to impulsive personality, obesity and cancer metastasis
  • Metabotropic Glutamate Receptor 3 (GRM3), which is involved in communication between neurons and long-term brain plasticity - a gene linked to psychiatric disorders, including schizophrenia and bipolar disorder
  • plus an additional 40 genes associated with lifetime cannabis use and four genes associated with frequency of cannabis use

• 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”;

• 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;

• 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 ¹⁹⁾
• 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.²⁰⁾
• 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 areas²¹⁾

• 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;

• 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;

• → 10 x risk of leukaemia in child;
• → lower birth weight, lower head circumference, high-pitched cries;
• → decr. development & behaviour change (all animal species studied);