Molecular Targets of the Phytocannabinoids: A Complex Picture

Summary & key facts

This review explains that cannabis makes many different natural chemicals called phytocannabinoids. More than 120 have been found. Some, like Δ9‑THC, act on the classic cannabinoid receptors CB1 and CB2. Others, like CBD, do not cause strong “highs” and act at many different molecular targets beyond CB1/CB2. The same phytocannabinoid can hit several targets, so their effects are complex and can vary by dose, cell type, and how they are tested in the lab.

Key facts:

• More than 120 phytocannabinoids have been isolated from Cannabis sativa L.
• Δ9‑THC is described in many studies as a moderate partial agonist at both CB1 and CB2 cannabinoid receptors.
• CBD is non‑psychotropic (it does not produce a strong “high”) and interacts with many targets, including GPR55 (antagonist), 5‑HT1A (agonist), TRP channels (agonist at TRPV1/2/3), and PPARγ (agonist).
• Phytocannabinoids act at many non‑cannabinoid targets. Examples include GPR55 and GPR18 (putative cannabinoid GPCRs), opioid and serotonin receptors, ion channels such as TRP and glycine receptors, and nuclear receptors like PPARγ.
• A single phytocannabinoid can have different actions at different targets: it may be an agonist at one receptor, an antagonist at another, or an allosteric modulator elsewhere. Effects also depend on cell type, receptor expression, and expe
• There are conflicting laboratory results for some targets. For example, studies differ on whether Δ9‑THC activates GPR55, likely due to differences in assays and cell systems.
• The review’s Table 1 lists pharmacology for common phytocannabinoids (Δ9‑THC, Δ8‑THC, CBN, CBD, CBG, CBC, THCV, CBDV, and others) and shows each has a distinct mix of targets and activities.

Topics

Cannabis and Cannabinoid Research GABA and Rice Research Neuroscience and Neuropharmacology Research

Categories

Health Sciences Medicine Pharmacology

Tags

Agonist Biochemistry Biology Botany Cannabidiol Cannabinoid Cannabinoid receptor Cannabis Cannabis sativa Chemistry Drug Hashish Illicit drug Medicine Pharmacology Psychiatry Receptor Traditional medicine

Substances

Cannabis

Conditions & symptoms

Anxiety Chronic Pain Anxiety or worry Chronic pain Poor appetite or overeating