Cannabinol

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Cannabinol
Cannabinol.svg
Cannabinol 3D.png
Legal status
Legal status
  • CA:Unscheduled
  • UK: Class B
  • US:Unscheduled
Identifiers
  • 6,6,9-Trimethyl-3-pentyl-benzo[c]chromen-1-ol
CAS Number
PubChem CID
IUPHAR/BPS
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.216.772 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C21H26O2
Molar mass 310.437 g·mol−1
3D model (JSmol)
Melting point 76–77 °C (169–171 °F) [1]
Solubility in water Insoluble in water, [2] soluble in methanol [3] and ethanol [4]  mg/mL (20 °C)
  • Oc2cc(cc1OC(c3c(c12)cc(cc3)C)(C)C)CCCCC
  • InChI=1S/C21H26O2/c1-5-6-7-8-15-12-18(22)20-16-11-14(2)9-10-17(16)21(3,4)23-19(20)13-15/h9-13,22H,5-8H2,1-4H3 Yes check.svgY
  • Key:VBGLYOIFKLUMQG-UHFFFAOYSA-N Yes check.svgY
 X mark.svgNYes check.svgY  (what is this?)    (verify)

Cannabinol (CBN) is a mildly psychoactive cannabinoid (e.g., CBD) that acts as a low affinity partial agonist at both CB1 and CB2 receptors. This activity at CB1 and CB2 receptors constitutes interaction of CBN with the endocannabinoid system (ECS).

Contents

In 1896 Cannabinol was first discovered in Cannabis by Thomas Barlow Wood, W.T Newton Spivey, and Thomas Easterfield. [5] In the early 1930s CBNs structure was identified by Robert Sidney Cahn. [6] [7] , marking the first development of a cannabis extract.

Its structure and chemical synthesis were achieved by 1940, followed by some of the first basic research studies to determine the effects of individual cannabis-derived compounds in vivo. Although CBN shares the same mechanism of action as other phytocannabinoids (e.g., Delta-9-tetrahydrocannabinol, Δ9-THC), it has a lower affinity for CB1 receptors, meaning that much higher doses of CBN are required in order to experience effects, such as mild sedation.

Chemical structure

Cannabinoid receptor agonists are categorized into four groups based on chemical structure. CBN, as one of the many phytocannabinoids derived from Cannabis Sativa L , is considered a classical cannabinoid. Other examples of compounds in this group include dibenzopyran derivatives such as Δ9-THC, well-known for underlying the subjective "high" experienced by cannabis users, as well as Δ8-THC, and their synthetic analogs. In contrast, endogenously produced cannabinoids (i.e., endocannabinoids), which also exert effects through CB agonism, are considered eicosanoids, distinguished by notable differences in chemical structure.

Compared to Δ9-THC, one additional aromatic ring confers CBN with a slower and more limited metabolic profile (see § CBN Formation & Metabolism). In contrast to THC, CBN has no double bond isomers nor stereoisomers. CBN can degrade into HU-345 from oxidation. In the case of oral administration of CBN, first-pass metabolism in the liver involves the addition of a hydroxyl group at C9 or C11, increasing the affinity and specificity of CBN for both CB1 and CB2 receptors (see 11-OH-CBN).

Synthesis and metabolism

This diagram represents the biosynthetic and metabolic pathways by which phytocannabinoids (e.g., CBD, THC, CBN) are created in the cannabis plant. Starting with CBG-A, the acidic forms of certain phytocannabinoids are generated via enzymatic conversion. From there, decarboxylation (i.e., catalyzed by combustion or heat) yields the most well-known metabolites present in the cannabis plant. CBN is unique in that it does not arise from a pre-existing acidic form, but rather is generated through the oxidation of THC.

CBN is unique among phytocannabinoids in that its biosynthetic pathway involves conversion directly from Δ9-THC, rather than from an acidic precursor form of CBN (e.g., Δ9-THC arises through decarboxylation of THC-A). CBN can be found in trace amounts in the Cannabis plant, found mostly in cannabis that is aged and stored, allowing for CBN formation through the oxidation of the cannabis plant's main psychoactive and intoxicating chemical, tetrahydrocannabinol (THC). This process of oxidation occurs via exposure to heat, oxygen, and/or light. Although reports are limited, CBN-A has also been measured at very low levels in the cannabis plant, thought to have formed via hydrolyzation of THC-A (see Phytocannabinoid Biosynthesis diagram, below).

This diagram represents the biosynthetic and metabolic pathways by which phytocannabinoids (e.g., CBD, THC, CBN) are created in the cannabis plant. Starting with CBG-A, the acidic forms of certain phytocannabinoids are generated via enzymatic conversion. From there, decarboxylation (i.e., catalyzed by combustion or heat) yields the most well-known metabolites present in the cannabis plant. CBN is unique in that it does not arise from a pre-existing acidic form, but rather is generated through the oxidation of THC. Phytocannabinoid Biosynthesis in Cannabis Sativa L.png
This diagram represents the biosynthetic and metabolic pathways by which phytocannabinoids (e.g., CBD, THC, CBN) are created in the cannabis plant. Starting with CBG-A, the acidic forms of certain phytocannabinoids are generated via enzymatic conversion. From there, decarboxylation (i.e., catalyzed by combustion or heat) yields the most well-known metabolites present in the cannabis plant. CBN is unique in that it does not arise from a pre-existing acidic form, but rather is generated through the oxidation of THC.

When administered orally, CBN demonstrates a similar metabolism to Δ9-THC, with the primary active metabolite produced through the hydrolyzation of C9 as part of first-pass metabolism in the liver. The active metabolite generated via this process is called 11-OH-CBN, which is 2x as potent as CBN, and has demonstrated activity as a weak CB2 antagonist. This metabolism starkly contrasts that of Δ9-THC in terms of potency, given that 11-OH-THC has been reported to have 10× the potency of Δ9-THC.

Due to high lipophilicity and first-pass metabolism, there is low bioavailability of CBN and other cannabinoids following oral administration. CBN metabolism is mediated in part by CYP450 isoforms 2C9 and 3A4. The metabolism of CBN may be catalyzed by UGTs (UDP-glucuronosyltransferases), with a subset of UGT isoforms (1A7, 1A8, 1A9, 1A10, 2B7) identified as potential substrates associated with CBN glucuronidation. The bioavailability of CBN following administration via inhalation (e.g., smoking or vaporizing) is approximately 40% that of intravenous administration.

Pharmacology

This timeline represents a simplified history of CBN with an emphasis on the complexity surrounding cannabis legislation in the US. Brief History of CBN (Emphasis on US Legislation).png
This timeline represents a simplified history of CBN with an emphasis on the complexity surrounding cannabis legislation in the US.

CBN was the first cannabis compound to be isolated from cannabis extract in the late 1800s. Its structure and chemical synthesis were achieved by 1940, followed by some of the first preclinical research studies to determine the effects of individual cannabis-derived compounds in vivo. [8]

Both THC and CBN activate the CB1 (Ki = 211.2 nM) and CB2 (Ki = 126.4 nM) receptors. [9] Each compound acts as a low affinity partial agonist at CB1 receptors with THC demonstrating 10–13× greater affinity to the CB1 receptor. [9] [10] [11] [8] [12] [13] Compared to THC, CBN has an equivalent or higher affinity to CB2 receptors, [9] [8] which are located throughout the central and peripheral nervous system, but are primarily associated with immune function. CB2 receptors are known to be located on immune cells throughout the body, including macrophages, T cells, and B cells. These immune cells have been shown to decrease production of immune-related chemical signals (e.g., cytokines) or undergo apoptosis as a consequence of CB2 agonism by CBN. [14] In cell culture, CBN demonstrates antimicrobial effects, particularly in instances of antibiotic-resistant bacteria. [15] CBN has also been reported to act as an ANKTM1 channel agonist at high concentrations (>20nM). [10] While some phytocannabinoids have been shown to interact with nociceptive and immune-related signaling via transient receptor potential channels (e.g., TRPV1 and TRPM8), there is currently limited evidence to suggest that CBN acts in this way. [10] [16] In preclinical rodent studies, CBN, anandamide and other CB1 agonists have demonstrated inhibitory effects on GI motility, reversible via CB1R blockade (i.e., antagonism). [10]

In considering the efficacy of cannabis-based products, there remains controversy surrounding a concept termed “the entourage effect”. This concept describes a widely reported but poorly-understood synergistic effect of certain cannabinoids when phytocannabinoids are coadministered with other naturally-occurring chemical compounds in the cannabis plant (e.g., flavonoids, terpenoids, alkaloids). This entourage effect is often cited to explain the superior efficacy observed in some studies of whole-plant-derived cannabis therapeutics as compared to isolated or synthesized individual cannabis constituents. [17]

Putative receptor targets

The table highlights several common cannabinoids along with putative receptor targets and therapeutic properties. Exogenous (plant-derived) phytocannabinoids are identified with an asterisk while remaining chemicals represent well-known endocannabinoids (i.e., endogenously produced cannabinoid receptor ligands).

Full NameKnown Receptor TargetsPutative Therapeutic Properties
*Cannabichromene (CBC)
  • Agonist at CB2, [18] TRPV3, and most potent phytocannabinoid at TRPA1 [18] [16]
  • Very low efficacy at TRPV1 and TRPV4, but may reduce expression of TRPV4 in the presence of inflammation [16]
  • High affinity for CB1 but no observed functional activity [18]
  • Antagonist at TRPM8 [16]
  • Antimicrobial and anti-inflammatory [18]
  • Potential neuroprotective effects [18]
  • Potential efficacy in treatment of inflammatory pain [18]
*Cannabidiol (CBD)
  • Very weak affinity for CB1 and CB2 [19]
  • Conflicting reports but generally described as negative allosteric modulator at CB1 & CB2, altering THC activity when THC & CBD are coadministered [19]
  • Agonist at TRPA1, [16] TRPV1 (high potency at this “capsaicin receptor” without ablative effects [16] ), TRPV2, TRPV3, PPARγ, 5-HT1A, A2 and A1 adenosine receptors [19]
  • Highest potency at TRPV1 [16]
  • Antagonist at GPR55, GPR18, 5-HT3A, [19] with highest potency as antagonist at TRPM8 [16]
  • Inverse agonist at GPR3, GPR6, and GPR12 [19]
  • Anti-inflammatory [20] [16]
  • Anti-convulsant [20]
  • Potential efficacy in treatment of inflammatory and chronic pain [16]
*Cannabigerol (CBG)
  • Low affinity agonist and partial agonist at CB1 and CB2, respectively [18]
  • Agonist at α2adrenoceptor [18] and TRP channels such as TRPA1, TRPV2, and TRPV3, with highest potency as agonist at TRPV1 [16]
  • Readily desensitizes but low affinity for TRPV4 [16]
  • Antagonist at 5-HT1A [18] and TRPM8 [16]
  • Anti-microbial, anti-inflammatory, and anti-nociceptive effects [18]
  • Neuroprotective properties via mitigation of oxidative stress [18]
  • Potential anti-tumor agent [18]
  • Potential efficacy in treatment of chemotherapy-induced muscle atrophy and weight loss [18]
*Cannabinol (CBN)
  • Agonist at CB1 and CB2, with some evidence of slightly higher affinity at CB2 [18]
  • Low affinity agonist at TRPV1, TRPV2, TRPV3, TRPV4, and TRPA1, [16] but readily desensitizes TRPV4 [16]
  • Antagonist at TRPM8 [16]
  • Antimicrobial and anti-inflammatory / immunosuppressive effects [18]
  • Potential efficacy in treatment of ocular disease and epidermolysis bullosa [18]
  • Reported neuroprotective effects (synergistic if coadministered with other cannabinoids) [18]
  • Relevance to pain, itch, and inflammation via TRP channel activity [18]
*Tetrahydrocannabinol (THC) / Delta-9-Tetrahydrocannabinol (Δ9-THC)
  • Agonist at CB1 and CB2, as well as GPR55, GPR18, PPARγ, and TRPA1 [16] [19]
  • Antagonist at TRPM8 [16] [19] and 5-HT3A [19]
  • Differing activity across TRP channels: highest potency phytocannabinoid at TRPV2; modest activity at TRPV3, TRPV4, TRPA1, and TRPM8; no activity observed at TRPV1 [16]
  • Importantly, 11-OH-THC, the active metabolite generated via first-pass-metabolism of THC, demonstrates different binding profile at TRP channels [16]
  • Potential relevance to sleep induction (e.g., increased adenosine levels [19] ) and increased quality of sleep [16]
  • Dose-dependent anxiolytic effects, [16] with anxiogenic effects at high doses
  • Appetite stimulation [16] [17]
  • Anti-nausea [16] [17]
  • In combination with CBD, potential efficacy in treatment of spasticity, neuropathic pain and muscle spasticity (see Sativex: THC-containing therapeutic approved in Europe as treatment for Multiple Sclerosis)
*2-Arachidonoylglycerol (2-AG)
  • Partial agonist at CB1 (e.g., on lysosomal surface, increasing lysosomal integrity) and CB2 [19]
  • Agonist at GPR55, GPR18, GPR119, PPAR, and robust activation at TRPV4 [16] [19]
  • Anti-oxidative properties [19]
  • Increased lysosomal stability & integrity [19]
  • Attenuation of mitochondrial damage during cell stress [19]
Anandamide (AEA)
  • Agonist at GPR18, GPR119, and PPAR, with robust activation at TRPV4, and very high efficacy at TRPA1 [16] [19]
  • Potent partial agonist at GPR55 [19] [17]
  • Low-affinity full agonist at TRPV1, [16] [17] with similar but less potent affinity as compared to capsaicin [16]
  • Antagonist at TRPM8 [16]
Anti-oxidative properties [19]

Neurotransmitter interactions

In the brain, the canonical mechanism of CB1 receptor activation is a form of short-term synaptic plasticity initiated via retrograde signaling of endogenous CB1 agonists such as 2AG or AEA (two primary endocannabinoids). DSI DSE Diagram - Mechanism of Action of eCB ligands at CB1R in the brain.jpg
In the brain, the canonical mechanism of CB1 receptor activation is a form of short-term synaptic plasticity initiated via retrograde signaling of endogenous CB1 agonists such as 2AG or AEA (two primary endocannabinoids).

In the brain, the canonical mechanism of CB1 receptor activation is a form of short-term synaptic plasticity initiated via retrograde signaling of endogenous CB1 agonists such as 2AG or AEA (two primary endocannabinoids). This mechanism of action is called depolarization-induced suppression of inhibition (DSI) or depolarization-induced suppression of excitation (DSE), [21] depending on the classification of the presynaptic neuron acted upon by the retrograde messenger (see diagram at left). In the case of CB1R agonism on the presynaptic membrane of a GABAergic interneuron, activation leads to a net effect of increased activity, while the same activity on a glutamatergic neuron leads to the opposite net effect. The release of other neurotransmitters is also modulated in this way, particularly dopamine, dynorphin, oxytocin, and vasopressin. [21]

Pharmacokinetics

A small study of six cannabis users found a highly variable half life of 32 ±  17 hours upon intravenous administration. [22] Similar to CBD, CBN is metabolized by the CYP2C9 and CYP3A4 liver enzymes and thus the half-life is sensitive to genetic factors that effect the levels of these enzymes. [23]

CBN is not listed in the schedules set out by the United Nations' Single Convention on Narcotic Drugs from 1961 nor their Convention on Psychotropic Substances from 1971, [24] so the signatory countries to these international drug control treaties are not required by these treaties to control CBN.

United States

According to the 2018 Farm Bill, [25] extracts from the Cannabis sativa L. plant, including CBN, are legal under US federal law as long as they have a delta-9 Tetrahydrocannabinol (THC) concentration of 0.3% or less, [26] [27] though sales or possession of CBN could potentially be prosecuted under the Federal Analogue Act. [28]

Related Research Articles

<span class="mw-page-title-main">Tetrahydrocannabinol</span> Chemical compound

Tetrahydrocannabinol (THC) is the principal psychoactive constituent of cannabis and one of at least 113 total cannabinoids identified on the plant. Although the chemical formula for THC (C21H30O2) describes multiple isomers, the term THC usually refers to the delta-9-THC isomer with chemical name (−)-trans-Δ9-tetrahydrocannabinol. THC is a terpenoid found in cannabis and, like many pharmacologically active phytochemicals, it is assumed to be involved in the plant's evolutionary adaptation against insect predation, ultraviolet light, and environmental stress. THC was first discovered and isolated by Israeli chemist Raphael Mechoulam in Israel in 1964. It was found that, when smoked, THC is absorbed into the bloodstream and travels to the brain, attaching itself to endocannabinoid receptors located in the cerebral cortex, cerebellum, and basal ganglia. These are the parts of the brain responsible for thinking, memory, pleasure, coordination and movement.

<span class="mw-page-title-main">Cannabinoid</span> Compounds found in cannabis

Cannabinoids are several structural classes of compounds found in the cannabis plant primarily and most animal organisms or as synthetic compounds. The most notable cannabinoid is the phytocannabinoid tetrahydrocannabinol (THC) (delta-9-THC), the primary psychoactive compound in cannabis. Cannabidiol (CBD) is also a major constituent of temperate cannabis plants and a minor constituent in tropical varieties. At least 113 distinct phytocannabinoids have been isolated from cannabis, although only four have been demonstrated to have a biogenetic origin. It was reported in 2020 that phytocannabinoids can be found in other plants such as rhododendron, licorice and liverwort, and earlier in Echinacea.

<span class="mw-page-title-main">Cannabinoid receptor</span> Group of receptors to cannabinoid compounds

Cannabinoid receptors, located throughout the body, are part of the endocannabinoid system of vertebrates– a class of cell membrane receptors in the G protein-coupled receptor superfamily. As is typical of G protein-coupled receptors, the cannabinoid receptors contain seven transmembrane spanning domains. Cannabinoid receptors are activated by three major groups of ligands: endocannabinoids; phytocannabinoids ; and synthetic cannabinoids. All endocannabinoids and phytocannabinoids are lipophilic.

<span class="mw-page-title-main">Tetrahydrocannabivarin</span> Homologue of tetrahydrocannabinol

Tetrahydrocannabivarin is a homologue of tetrahydrocannabinol (THC) having a propyl (3-carbon) side chain instead of pentyl (5-carbon), making it non-psychoactive in lower doses. It has been shown to exhibit neuroprotective activity, appetite suppression, glycemic control and reduced side effects compared to THC, making it a potential treatment for management of obesity and diabetes. THCV was studied by Roger Adams as early as 1942.

<span class="mw-page-title-main">WIN 55,212-2</span> Chemical compound

WIN 55,212-2 is a chemical described as an aminoalkylindole derivative, which produces effects similar to those of cannabinoids such as tetrahydrocannabinol (THC) but has an entirely different chemical structure.

<span class="mw-page-title-main">11-Hydroxy-THC</span> Chemical compound

11-Hydroxy-Δ9-tetrahydrocannabinol, usually referred to as 11-hydroxy-THC is the main active metabolite of tetrahydrocannabinol (THC), which is formed in the body after Δ9-THC is consumed.

<span class="mw-page-title-main">Cannabigerol</span> Minor cannabinoid

Cannabigerol (CBG) is one of more than 120 identified cannabinoid compounds found in the plant genus Cannabis. Cannabigerol is the decarboxylated form of cannabigerolic acid, the parent molecule from which other cannabinoids are synthesized.

<span class="mw-page-title-main">Tetrahydrocannabutol</span> Chemical compound

Δ9-Tetrahydrocannabutol is a phytocannabinoid found in cannabis that is a homologue of tetrahydrocannabinol (THC), the main active component of Cannabis. Structurally, they are only different by the pentyl side chain being replaced by a butyl side chain. THCB was studied by Roger Adams as early as 1942

<span class="mw-page-title-main">JWH-073</span> Chemical compound

JWH-073, a synthetic cannabinoid, is an analgesic chemical from the naphthoylindole family that acts as a full agonist at both the CB1 and CB2 cannabinoid receptors. It is somewhat selective for the CB1 subtype, with affinity at this subtype approximately 5× the affinity at CB2. The abbreviation JWH stands for John W. Huffman, one of the inventors of the compound.

<span class="mw-page-title-main">Cannabichromene</span> Chemical compound

Cannabichromene (CBC), also called cannabichrome, cannanbichromene, pentylcannabichromene or cannabinochromene, exhibits anti-inflammatory properties in vitro, which may, theoretically, contribute to cannabis analgesic effects. It is a phytocannabinoid, one of the hundreds of cannabinoids found in the Cannabis plant. It bears structural similarity to the other natural cannabinoids, including tetrahydrocannabinol (THC), tetrahydrocannabivarin (THCV), cannabidiol (CBD), and cannabinol (CBN), among others. CBC and cannabinols are present in cannabis. It is not scheduled by the Convention on Psychotropic Substances.

A cannabinoid receptor antagonist, also known simply as a cannabinoid antagonist or as an anticannabinoid, is a type of cannabinoidergic drug that binds to cannabinoid receptors (CBR) and prevents their activation by endocannabinoids. They include antagonists, inverse agonists, and antibodies of CBRs. The discovery of the endocannabinoid system led to the development of CB1 receptor antagonists. The first CBR inverse agonist, rimonabant, was described in 1994. Rimonabant blocks the CB1 receptor selectively and has been shown to decrease food intake and regulate body-weight gain. The prevalence of obesity worldwide is increasing dramatically and has a great impact on public health. The lack of efficient and well-tolerated drugs to cure obesity has led to an increased interest in research and development of CBR antagonists. Cannabidiol (CBD), a naturally occurring cannabinoid and a non-competitive CB1/CB2 receptor antagonist, as well as Δ9-tetrahydrocannabivarin (THCV), a naturally occurring cannabinoid, modulate the effects of THC via direct blockade of cannabinoid CB1 receptors, thus behaving like first-generation CB1 receptor inverse agonists, such as rimonabant. CBD is a very low-affinity CB1 ligand, that can nevertheless affect CB1 receptor activity in vivo in an indirect manner, while THCV is a high-affinity CB1 receptor ligand and potent antagonist in vitro and yet only occasionally produces effects in vivo resulting from CB1 receptor antagonism. THCV has also high affinity for CB2 receptors and signals as a partial agonist, differing from both CBD and rimonabant.

<span class="mw-page-title-main">Tetrahydrocannabinolic acid</span> Chemical compound

Tetrahydrocannabinolic acid is a precursor of tetrahydrocannabinol (THC), an active component of cannabis.

The entourage effect is a hypothesis that cannabis compounds other than tetrahydrocannabinol (THC) act synergistically with it to modulate the overall psychoactive effects of the plant.

<span class="mw-page-title-main">Tetrahydrocannabiphorol</span> Chemical compound

Tetrahydrocannabiphorol (THCP) is a potent phytocannabinoid, a CB1 and CB2 agonist which was known as a synthetic homologue of THC, but for the first time in 2019 was isolated as a natural product in trace amounts from Cannabis sativa. It is structurally similar to Δ9-THC, the main active component of cannabis, but with the pentyl side chain extended to heptyl. Since it has a longer side chain, its cannabinoid effects are "far higher than Δ9-THC itself." Tetrahydrocannabiphorol has a reported binding affinity of 1.2 nM at CB1, approximately 33 times that of Δ9-THC (40 nM at CB1). THCP was studied by Roger Adams as early as 1942.

<span class="mw-page-title-main">Δ-8-Tetrahydrocannabinol</span> Isomer of tetrahydrocannabinol

Δ-8-tetrahydrocannabinol is a psychoactive cannabinoid found in the Cannabis plant. It is an isomer of delta-9-tetrahydrocannabinol, the compound commonly known as THC.

<span class="mw-page-title-main">Tetrahydrocannabiorcol</span> Chemical compound

Δ9-Tetrahydrocannabiorcol (Δ9-THCC, (C1)-Δ9-THC) is a phytocannabinoid found in Cannabis pollen. It is a homologue of THC and THCV with the alkyl side chain replaced by a smaller methyl group. Unlike THC and THCV, THCC has negligible affinity for the CB1 and CB2 cannabinoid receptors because of the smaller methyl group and does not have psychoactive effects as a result, but conversely it is significantly more potent than THC or THCV as an activator of the TRPA1 calcium channel which plays an important role in pain perception, and it has been shown to produce analgesic effects via activation of spinal TRPA1 channels. THCC was studied by Roger Adams as early as 1942.

<span class="mw-page-title-main">Hexahydrocannabinol</span> Hydrogenated derivative of THC

Hexahydrocannabinol (HHC) is a hydrogenated derivative of tetrahydrocannabinol (THC). It is a naturally occurring phytocannabinoid that has rarely been identified as a trace component in Cannabis sativa, but can also be produced synthetically by hydrogenation of cannabis extracts. The synthesis and bioactivity of HHC was first reported in 1940 by Roger Adams using tetrahydrocannabinol prepared from cannabidiol.

<span class="mw-page-title-main">11-Hydroxyhexahydrocannabinol</span> Chemical compound

11-Hydroxyhexahydrocannabinol is an active metabolite of tetrahydrocannabinol (THC) and a metabolite of the trace cannabinoid hexahydrocannabinol (HHC).

<span class="mw-page-title-main">Tetrahydrocannabihexol</span> Chemical compound

Tetrahydrocannabihexol is a phytocannabinoid, the hexyl homologue of tetrahydrocannabinol (THC) which was first isolated from Cannabis plant material in 2020 along with the corresponding hexyl homologue of cannabidiol, though it had been known for several decades prior to this as an isomer of the synthetic cannabinoid parahexyl. Another isomer Δ8-THCH is also known as a synthetic cannabinoid under the code number JWH-124, though it is unclear whether this occurs naturally in Cannabis, but likely is due to Delta-8-THC itself being a degraded form of Delta-9-THC. THC-Hexyl can be synthesized from 4-Hexylresorcinol and was studied by Roger Adams as early as 1942.

Cannabinoids are compounds found in the cannabis plant or synthetic compounds that can interact with the endocannabinoid system. The most notable cannabinoid is the phytocannabinoid tetrahydrocannabinol (THC) (Delta-9-THC), the primary intoxicating compound in cannabis. Cannabidiol (CBD) is another major constituent of some cannabis plants. At least 113 distinct cannabinoids have been isolated from cannabis.

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  17. 1 2 3 4 5 Legare CA, Raup-Konsavage WM, Vrana KE (2022). "Therapeutic Potential of Cannabis, Cannabidiol, and Cannabinoid-Based Pharmaceuticals". Pharmacology. 107 (3–4): 131–149. doi: 10.1159/000521683 . PMID   35093949.
  18. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 Sampson PB (January 2021). "Phytocannabinoid Pharmacology: Medicinal Properties of Cannabis sativa Constituents Aside from the "Big Two"". Journal of Natural Products. 84 (1): 142–160. doi:10.1021/acs.jnatprod.0c00965. PMID   33356248. S2CID   229694293.
  19. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 Cherkasova V, Wang B, Gerasymchuk M, Fiselier A, Kovalchuk O, Kovalchuk I (October 2022). "Use of Cannabis and Cannabinoids for Treatment of Cancer". Cancers. 14 (20): 5142. doi: 10.3390/cancers14205142 . PMC   9600568 . PMID   36291926.
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  24. ↑ "UN International Drug Control Conventions". United Nations Office on Drugs and Crime. United Nations Commission on Narcotic Drugs. Archived from the original on March 17, 2014. Retrieved February 15, 2017.
  25. ↑ Office of the Commissioner (October 18, 2021). "FDA Regulation of Cannabis and Cannabis-Derived Products, Including Cannabidiol (CBD)". FDA.
  26. ↑ Mead A (May 2017). "The legal status of cannabis (marijuana) and cannabidiol (CBD) under U.S. law". Epilepsy & Behavior. 70 (Pt B): 288–291. doi: 10.1016/j.yebeh.2016.11.021 . PMID   28169144.
  27. ↑ "Section 1308.11 Schedule I". Code of Federal Regulations. Office of Diversion Control, Drug Enforcement Administration, U.S. Department of Justice. Archived from the original on February 9, 2012.
  28. ↑ "Federal Controlled Substance Analogue Act Summary". Erowid Analog Law Vault. January 2001.
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