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. 2023 Aug 21;11(8):2323. doi: 10.3390/biomedicines11082323

Table A1.

Selected Cannabis sativa L.-derived cannabinoids, their targets, mechanisms of action, and potential resultant pharmacological effects.

Targets Mechanisms of Action Potential Pharmacological Effects References
Δ9-Tetrahydrocannabinol (THC)
CB1 Partial agonist Analgesic **,***
Anti-convulsant **
Anti-epileptic **
Sleep improvement **,***
Anti-anorectic, appetite stimulating **,***
Anti-emetic **,***
Anxiolytic **		 [27,93,94,95,96,97,98,99,100,101,102]
CB2 Partial agonist Analgesic **,*** [94,95]
GPR55 Agonist Not reported [103]
GPR18 Agonist Not reported * [104,105]
5-HT-3A Antagonist Anti-nociception *
Anti-emetic *		 [106,107]
DOR (Negative)
Allosteric modulator		 Not reported [108,109]
MOR (Negative)
Allosteric modulator		 Not reported [108,109]
PPAR-y Agonist Anti-cancer, anti-proliferative *,** [110]
GlyR Agonist Analgesic *,** [111]
TRPV2 Agonist Not reported [32]
TRPV3 Agonist Not reported [32,112]
TRPV4 Agonist Not reported [32,112]
TRPA1 Agonist Not reported [113]
TRPM8 Antagonist Not reported [113]
Cannabidiol (CBD)
CB1 Negative allosteric modulator
Antagonist		 THC-related adverse effects modulation **,***
Anxiolytic **
Antidepressant **
Vasorelaxant **		 [27,28,95,114,115,116,117,118,119,120,121]
CB2 Partial agonist
Negative allosteric modulator
Antagonist		 Seizure reduction **
Anti-epileptic **
Anti-inflammatory **
Anti-cancer *,**
Body weight decrease **
Neuroprotection **		 [27,95,114,115,122,123,124,125,126]
GPR3 Inverse agonist Alzheimer’s disease improvement * [127,128]
GPR6 Inverse agonist Parkinson’s disease improvement * [127,128]
GPR12 Inverse agonist Anti-cancer * [127,129]
GPR55 Antagonist Anti-epileptic **,***
Seizure dampening **
Bone resorption inhibition **
Parkinson’s motor skills improvement **
Cancer cell migration inhibition *		 [103,130,131,132,133,134]
FAAH Inhibitor AEA increase and related effects *
Sleep induction *,**
Stress reduction ***
Anxiolytic ***
Anti-depressant **		 [135,136,137,138]
5-HT-1A Agonist
Inverse agonist		 Anti-emetic *,**
Analgesic **
Chemotherapy induced neuropathic pain reduction *,**
Anxiolytic **
Anti-depressant **
Cognitive performance improvement **
Anti-epileptic *,**,***
Seizure reduction **
Anti-stress **
Neuroprotection **		 [117,126,139,140,141,142,143,144,145,146,147,148,149,150]
5-HT-3A Antagonist Anti-emetic **
Cardiovascular effects ** 		[151,152]
A1A Agonist Anti-arrhythmic **
Analgesic **		 [153,154]
A2A Agonist Anti-inflammatory *,**
Cognitive performance improvement **		 [155,156,157]
PPAR-γ Agonist β-amyloid-induced neuroinflammation
reduction *,**
Hippocampal neurogenesis *,**
Alzheimer’s disease improvement *,**		 [158]
Immune cell
(not further specified)		 Inhibitor
Activator		 Anti-inflammatory *,**
Immunosuppressive *,**
Cytokine release reduction/increase *,**
Anti-arthritic **
Multiple sclerosis amelioration **		 [159,160,161]
GlyR-α1 Positive allosteric modulator
Agonist		 Anti-inflammatory *
Neuroprotective *		 [162]
GlyR-α3 Positive allosteric modulator Analgesic ** [163]
GABA-A Positive allosteric modulator Anti-convulsant **
Anti-epileptic **		 [130,164]
TRPV1 Agonist Neuron anti-hyperexcitability *
Anxiolytic **
Anti-cancer, apoptosis *
Microglial phagocytosis enhancement *
Cardiovascular effects **		 [32,135,152,165,166,167,168]
TRPV2 Agonist Microglial phagocytosis enhancement * [32,168]
TRPV3 Agonist Not reported [112]
TRPV4 Agonist Not reported [112]
TRPA1 Agonist Analgesic ** [32,113,154]
TRPM8 Antagonist Not reported [113]
DOR (Negative)
Allosteric modulator		 Not reported [108,109]
MOR (Negative)
Allosteric modulator		 Not reported [108,109]
D2 Partial agonist Anti-psychotic * [169]
Cannabigerol (CBG)
CB2 Partial agonist Anti-inflammatory *,**
Colitis attenuation *,**		 [170,171]
AEA uptake Inhibitor Various effects related to AEA * [32]
5-HT-1A Antagonist Reverse anti-emetic effect of, e.g., CBD ** [150,172]
A2A Agonist Not reported [172]
TRPV1 Agonist Not reported [32]
TRPA1 Agonist Not reported [32,113]
TRPM8 Antagonist Colon anti-cancer ** [32,113,173]
Cannabichromene (CBC)
CB2 Agonist Anti-inflammatory * [174]
AEA uptake Inhibitor Various effects related to AEA *
Analgesic **		 [32,154]
TRPV3 Agonist Not reported [32,112]
TRPV4 Agonist Not reported [32,112]
TRPA1 Agonist Anti-inflammatory **
Colitis reduction **
Analgesic **		 [32,113,154,175]
TRPM8 Antagonist Not reported [32,113]
Cannabinol (CBN)
CB1 Agonist Appetite increase ** [176,177]
CB2 Agonist
Inverse agonist		 Not reported [176,178]
TRPA1 Agonist Not reported [32]
TRPM8 Antagonist Not reported [32]
Δ9-Tetrahydrocannabivarin (THCV)
CB1 Agonist
Antagonist		 Anti-psychoactive (e.g., reverse THC-induced psychoactive effects) **
Analgesic **
Anti-convulsant **
Anti-epileptic *
Hypophagia and weight reduction**
Glycemic control improvement**,***		 [95,179,180,181,182,183,184,185]
CB2 Partial agonist
Antagonist		 Anti-inflammatory **
Inflammatory pain reduction **		 [95,179,181]
5-HT-1A Agonist Antipsychotic *,** [186]
TRPV2 Agonist Not reported [32]
TRPA1 Agonist Not reported [32]
TRPM8 Antagonist Not reported [32]
Cannabidivarin (CBDV)
GABA-A Positive allosteric modulator Anti-convulsive *,***
Anti-epileptic *,***		 [187]
TRPV1 Agonist Neuronal anti-hyperexcitability *
Anti-convulsant **		 [32,165,188]
TRPV2 Agonist Not reported [32]
TRPV3 Agonist Not reported [32,112]
TRPA1 Agonist Not reported [32]
Δ-9-Tetrahydrocannabinolic acid (THCA)
CB1 Partial agonist Anti-nociceptive **
Anti-inflammatory **		 [27]
CB2 Agonist Not reported [27]
PPAR-γ Agonist Adiposity reduction **
Metabolic syndrome prevention **
Anti-inflammatory **
Neuroprotective *,**		 [189,190]
Cannabidiolic acid (CBDA)
CB2 Partial agonist Not reported [27,80]
5-HT-1A Agonist Anti-emetic **
Anti-convulsant **
Anxiolytic **		 [191,192,193]
TRPV1 Agonist Anti-hyperalgesic ** [32,93]
Δ8-Tetrahydrocannabinol (Δ8-THC)
CB1 Partial agonist Appetite stimulant ** [194,195]
CB2 Agonist Not reported [194]

*: Pre-clinical in vitro study; **: pre-clinical in vivo study; ***: clinical study; N.B.: This table is non-exhaustive, broadly elucidating selected compounds and some of their potential pharmacological effects currently present in the pre-clinical literature. Depending on study parameters, the compounds show differing, sometimes biphasic, affinities and effects at different targets, thus highlighting the contradictory and equivocal evidence state. For a more extensive review on cannabinoid mechanisms of action and pharmacological effects, see these extensive reviews on the subject: Morales et al. [24], Stasiulewicz et al. [196], Almeida et al. [197], Oultram et al. [198], Vitale et al. [25], Peng et al. [199], Matheson et al. [200], Odieka et al. [71], and Castillo-Arellano et al. [26]. Abbreviations: 5-hydroxytryptamine receptor 1A (5-HT-1A); 5-hydroxytryptamine receptor 3A (5-HT-3A); adrenergic receptor alpha-1 (A1A); adrenergic receptor alpha-2 (A2A); anandamide endocannabinoid (AEA); cannabinoid receptor 1 (CB1); cannabinoid receptor 2 (CB2); delta-opioid receptor (DOR); dopamine D2 receptor (D2); fatty acid amide hydrolase enzyme (FAAH); gamma-aminobutyric acid type A receptor (GABA-A); glycine receptor (GlyR); glycine receptor type α 1 (GlyR-α1); glycine receptor type α 3 (GlyR-α3); G-protein-coupled receptor 2 (GPR2); G-protein-coupled receptor 3 (GPR3); G-protein-coupled receptor 6 (GPR6); G-protein-coupled receptor 12 (GPR12); G-protein-coupled receptor 18 (GPR18); G-protein-coupled receptor 55 (GPR55); Mu-opioid receptor (MOR); peroxisome proliferator-activated receptor gamma (PPAR-γ); transient receptor potential cation channel type A1 (TRPA1); transient receptor potential cation channel 8 (TRPM8); transient receptor potential vanilloid type 1 (TRPV1); transient receptor potential vanilloid type 2 (TRPV2); transient receptor potential vanilloid type 3 (TRPV3); transient receptor potential vanilloid type 4 (TRPV4).