Cannabinoids

Cannabinoids are a class of structurally related compounds — terpenophenolic molecules combining a terpene-derived isoprenoid moiety with a phenolic ring system — produced principally in the glandular trichomes (small resin-secreting hairs) on the flowers and surrounding leaves of [[cannabis|Cannabis sativa]]. Approximately 100+ distinct cannabinoids have been identified in the plant, of which the two most abundant and best-studied are THC and CBD.

The principal cannabinoids

A non-exhaustive list, with brief notes on each:

• THC (delta-9-tetrahydrocannabinol). The principal psychoactive cannabinoid. Binds strongly to CB1 receptors in the central [[nervous-system|nervous system]], producing the characteristic high of [[cannabis|marijuana]]. Substantial therapeutic applications (pain, nausea, appetite stimulation, spasticity); substantial regulatory complications. Industrial hemp is legally defined in the U.S. (post-2018 Farm Bill) as Cannabis sativa with ≤0.3% delta-9 THC by dry weight.
• CBD (cannabidiol). The principal non-psychoactive cannabinoid; the most abundant cannabinoid in industrial-hemp varieties. Does not bind strongly to CB1 (does not produce a high) but interacts with the [[endocannabinoid-system|endocannabinoid system]] through CB2 receptors and various other mechanisms. Substantial documented anticonvulsant effect (FDA-approved as Epidiolex for Lennox-Gastaut and Dravet syndromes); active research on anxiety, inflammation, sleep, and other applications. The cannabinoid principally driving the contemporary U.S. hemp-extract market.
• CBG (cannabigerol). The chemical precursor from which most other cannabinoids derive — CBG is converted in the plant by specific enzymes into THC, CBD, or CBC, depending on which enzymatic pathway is dominant in the variety. Present in low concentrations in mature plants but available through specific cultivars or harvest timing.
• CBN (cannabinol). A degradation product of THC, formed by oxidation. Mildly psychoactive; documented sedative effects.
• CBC (cannabichromene). Non-psychoactive; emerging research on inflammation and neurogenesis.
• THCV (tetrahydrocannabivarin). Structural variant of THC with different receptor binding profile; appetite-suppressant effects documented (in contrast to THC’s appetite-stimulating effects).
• CBDV (cannabidivarin). Structural variant of CBD; emerging research on epilepsy and neurodevelopmental conditions.
• The acidic precursors. In the living plant, cannabinoids exist primarily as their acid forms (THCA, CBDA, CBGA, etc.) and convert to the neutral forms through decarboxylation triggered by heat, light, or extended storage. Raw fresh [[cannabis|cannabis]] contains principally the acid forms; smoking or cooking decarboxylates them.

The endocannabinoid system

The human [[endocannabinoid-system|endocannabinoid system]] is the regulatory network that cannabinoids interact with. Its existence was discovered through cannabinoid research — researchers attempting to understand how THC produced its effects identified first the CB1 receptor (1988, in rat brain), then CB2 (1993, principally in immune tissue), then the endogenous ligands the body produces to bind these receptors (anandamide, 1992; 2-arachidonoylglycerol, 1995), then the metabolic enzymes that produce and degrade those ligands. The system turns out to be substantially foundational — modulating pain, mood, appetite, sleep, memory, immune response, reproductive function, and many other dimensions of physiology. See [[endocannabinoid-system]] for detail.

Therapeutic applications

The current state of cannabinoid medicine, in summary:

• FDA-approved. Epidiolex (CBD) for Lennox-Gastaut and Dravet syndromes (rare childhood epilepsies); Marinol/Syndros (synthetic THC) for chemotherapy-induced nausea and HIV/AIDS-related anorexia; Cesamet (synthetic THC analog) for similar applications. Sativex (THC + CBD oromucosal spray) is approved in many countries (not the U.S.) for multiple sclerosis spasticity.
• Substantial evidence. Pain (chronic, neuropathic), nausea/vomiting (chemotherapy-induced), spasticity (multiple sclerosis), epilepsy.
• Moderate evidence. Anxiety, sleep, PTSD-related conditions, inflammation.
• Emerging evidence. Various neurodegenerative conditions, autoimmune conditions, neurodevelopmental conditions.
• Substantial research limitations. U.S. federal Schedule I status of [[cannabis|cannabis]] (which is in tension with state-level legalization and with the legal status of hemp-derived CBD) has substantially complicated research; much of the strongest evidence comes from Israel, Canada, and Europe.

The hemp/marijuana distinction

In legal terms (U.S., post-[[2018-farm-bill-hemp-provisions|2018 Farm Bill]]): hemp is [[cannabis|Cannabis sativa]] with ≤0.3% delta-9 THC by dry weight; marijuana is Cannabis sativa with >0.3%. The distinction is regulatory, not biological — both are the same plant species. Industrial-hemp varieties are bred for low THC and (often) high CBD; marijuana varieties for high THC. The 0.3% threshold is somewhat arbitrary (it derives from a 1976 Canadian taxonomic publication, not from any pharmacological or agricultural significance).

Honest framing

A few notes for clarity:

• The hype/skepticism axis. CBD and broader cannabinoid medicine have been substantially over-marketed (CBD is not a cure for everything) and substantially under-researched (the conventional medical and regulatory establishments have been slow to take cannabinoid medicine seriously). [[0mn1one|The platform]]‘s posture: take the documented clinical evidence as it is; do not amplify either the over-claims or the dismissals.
• Quality control. The U.S. CBD market has substantial quality-control problems — products often contain different cannabinoid profiles than the label claims; some contain solvent residues, heavy-metal contamination, or unlabeled THC. Third-party testing matters substantially.
• Drug interactions. CBD inhibits several cytochrome-P450 enzymes that metabolize many common medications; substantial drug interactions can result. Anyone using CBD with prescription medications should consult a clinician.
• THC and adolescent development. Substantial evidence that regular THC use during adolescence affects brain development. [[0mn1one|The platform]]‘s posture: no judgment on adult use; substantial caution about adolescent use.

See also

Auto-generated from this entry’s typed relations: frontmatter, grouped by relation type so the editorial signal isn’t flattened.

• Subset of: [[hemp]]
• Parallels: [[endocannabinoid-system]]
• Member of: [[compound]]

Sources

1. Handbook of [[cannabis|Cannabis]]. Ed. Roger Pertwee. Oxford, 2014. Source class: handbook / definitive contemporary scholarly reference.
2. Raphael Mechoulam et al. — various foundational publications. (Mechoulam was the principal discoverer of THC structure (1964) and CBD-receptor interactions; the foundational figure of cannabinoid chemistry.) Source class: scholarly literature.
3. National Academies of Sciences. The Health Effects of [[cannabis|Cannabis]] and Cannabinoids. National Academies Press, 2017. Source class: scholarly survey / definitive contemporary review.
4. Epidiolex (cannabidiol) prescribing information. GW Pharmaceuticals / Jazz Pharmaceuticals. Source class: regulatory documentation.

Lenses still to grow

• CBD as separate substantial topic.
• THC as separate substantial topic.
• Raphael Mechoulam as person entry — the foundational figure.
• The entourage effect — the question of whole-plant vs. isolated-cannabinoid medicine.
• The U.S. regulatory situation in detail.
• Quality-control as continuing market issue.