Cannabinoid

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A flowering cannabis plant, the most common source of cannabinoids.
A bag of Spice brand herbal incense. This contains synthetic cannabinoids which produce a similar effect to that of cannabis.

A cannabinoid is one of a class of diverse chemical compounds that act on cannabinoid receptors on cells that alter neurotransmitter functioning in the brain. These receptor proteins include the endocannabinoids (produced naturally in the body by humans and animals),[1] the phytocannabinoids (found in cannabis and some other plants), and synthetic cannabinoids (manufactured chemically).

The most notable cannabinoid is the phytocannabinoid ∆9-tetrahydrocannabinol (THC), the primary psychoactive compound of cannabis.[2][3] Cannabidiol (CBD) is another major constituent of the plant, representing up to 40% in extracts of the plant resin.[4] There are at least 85 different cannabinoids isolated from cannabis which exhibit varied effects.

Synthetic cannabinoids encompass a variety of distinct chemical classes: the classical cannabinoids structurally related to THC; the nonclassical cannabinoids (cannabimimetics) including the aminoalkylindoles, 1,5-diarylpyrazoles, quinolines, and arylsulphonamides; and eicosanoids related to the endocannabinoids.[2][3]

Cannabinoid receptors

Before the 1980s, it was often speculated that cannabinoids produced their physiological and behavioral effects via nonspecific interactions instead of interacting with specific receptors directly. The discovery of the first cannabinoid receptors in the 1980s helped to resolve this debate. These receptors are common in animals and have been found in mammals, birds, fish, and reptiles. At present, there are two known types of cannabinoid receptors, termed CB1 and CB2,[1] with mounting evidence of more.[5][6] However, the role of these interactions and how they result in the cannabinoid high experience continues to remain elusive.

Cannabinoid receptor type 1

CB1 receptors are found primarily in the brain, more specifically in the basal ganglia and in the limbic system (including the hippocampus).[1] They are also found in the cerebellum and in both male and female reproductive systems. CB1 receptors are absent in the medulla oblongata, the part of the brain stem responsible for respiratory and cardiovascular functions. Thus, there is not the risk of respiratory or cardiovascular failure that can be produced by some drugs. CB1 receptors appear to be responsible for the euphoric and anticonvulsive effects of cannabis. However, the role of these interactions and how they result in the cannabinoid high experience continues to remain elusive.

Cannabinoid receptor type 2

CB2 receptors are predominantly found in the immune system, or immune-derived cells[7] with the greatest density in the spleen. While found only in the peripheral nervous system, a report does indicate that CB2 is expressed by a subpopulation of microglia in the human cerebellum.[8] CB2 receptors appear to be responsible for the anti-inflammatory and possibly other therapeutic effects of cannabis.[7] However, the role of these interactions and how they result in the cannabinoid high experience continues to remain elusive.

Subjective effects

Disclaimer: The effects listed below cite the Subjective Effect Index (SEI), an open research literature based on anecdotal user reports and the personal analyses of PsychonautWiki contributors. As a result, they should be viewed with a healthy degree of skepticism.

It is also worth noting that these effects will not necessarily occur in a predictable or reliable manner, although higher doses are more liable to induce the full spectrum of effects. Likewise, adverse effects become increasingly likely with higher doses and may include addiction, severe injury, or death ☠.


Physical effects
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Visual effects
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Cognitive effects
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Auditory effects
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Phytocannabinoids

Comparison of phytocannabinoids

Phytocannabinoids can be defined as any plant-derived natural product capable of either directly interacting with cannabinoid receptors or sharing chemical similarity with cannabinoids or both. The entourage effect is a proposed mechanism by which compounds present in cannabis which are largely non-psychoactive by themselves modulate the overall psychoactive effects of the plant (these resulting principally from the action of the main psychoactive component of cannabis, tetrahydrocannabinol (THC)).

Phytocannabinoid ← phytocannabinoid acid

Quasi-psychedelic phytocannabinoids

  • Δ-8-THC. Psychoactive, but about half as potent as Δ-9-THC.
    • Decarboxylation: Δ-8-THCA → Δ-8-THC -- only trace amounts exist in cannabis
    • Chemical conversion: CBD + acid 8 h → 50% Δ-8-THC
  • Δ-9-THC (THC). Most abundant psychoactive component of cannabis. Is the standard when comparing THC analogs.
  • Δ-10-THC. Psychoactive, but less potent than Δ-8-THC.
    • Decarboxylation: Δ-10-THCA → Δ-10-THC-- only trace amounts exist in cannabis
    • Chemical conversion: CBD + acid
  • THCH (more info). 25 times more potent than THC.
    • Decarboxylation: THCHA → THCH -- only trace amounts exist in cannabis
    • Chemical conversion: CBDH + acid
  • THCP (more info). 30 times more potent than THC.
    • Biosynthesis: CBGPA → THCPA → THCP[17]
    • Decarboxylation: THCPA → THCP-- only trace amounts exist in cannabis
    • Chemical conversion: CBDP + acid

Quasi-psychedelic phytocannabinoids synthesized through chemical modification

  • AcO-THC (aka THC-O-acetate). 3-5 times more potent than THC.
    • Metabolization: THCAO is a prodrug, meaning it requires metabolization in order to take effect. It metabolically undergoes an activation process of converting to THC through de-acetylation, then THC continues into its own primary metabolites similarly to THC's oral route. Because of this, the onset when smoked can be significantly longer ranging from 20-45 minutes, but not as long as ingesting THC orally in comparison. THCAO through the oral route can also have longer onsets than oral THC due to its extra metabolic processes, with an onset of around 90 minutes.[18]
    • Decarboxylation: Lack of information on decarboxylation, but it can be inferred that it decarboxylates like its normal parent compound since research suggests that heating it at 340°C (644°F) unbinds the acetyl group, releasing toxic ketene gas.[19]
    • Chemical conversion: acetic anhydride + Δ-9-THC/Δ-8-THC → Δ-9-THCAO/Δ-8-THCAO, respectively.[20]

Non-quasi-psychedelic phytocannabinoids, some which can be synthesized to quasi-psychedelic cannabinoids with biosynthesis or chemical conversion (see above)

  • CBCCBCA
  • CBCVCBCVA
  • CBD
    • Biosynthesis: CBGA → CBDA → CBD[21]
    • Decarboxylation: CBDA → CBD
    • Chemical conversion: THC + iodine → CBD
  • CBDD
  • CBDVCBDVA
  • CBDH
  • CBDP
    • Biosynthesis: CBGPA → CBDPA → CBDP[22]
    • Decarboxylation: CBDPA → CBDP
  • CBECBEA
  • CBG
  • CBGMCBGAM
  • CBGVCBGVA
  • CBLCBLA
  • CBLVCBLVA
  • CBNCBNA
  • CBTCBTA
  • CBVCBVA
  • THCCTHCCA
    • Despite sounding a lot like THC, THCC is more similar to CBD than it is to THC
  • THCVTHCVA
    • THCV is non-psychoactive.[23]

Plant sources

Synthetic cannabinoids

Main article: Synthetic cannabinoid

Synthetic cannabinoids are any artificial compound which is functionally similar to Δ9-tetrahydrocannabinol (THC), the active principle of cannabis. Like THC, they bind to the same cannabinoid receptors in the brain and are often sold as legal alternatives.

Toxicity and harm potential

Unlike cannabis, there have been multiple deaths[24][25][26][27][28][29][30] associated with the repeated abuse of synthetic cannabinoids as well as serious side effects resulting from its long-term use.[31][32][33] Therefore, it is strongly discouraged to take this substance for extended periods of time or in excessive doses. Compared to cannabis and its active cannabinoid THC, the adverse effects are often much more severe and can include high blood pressure, increased heart rate, heart attacks,[34][35] agitation,[36] vomiting,[37][38][39] hallucinations,[40] psychosis,[41][42][36][43] seizures,[44][45][46] and convulsions[47][48] as well as many others. Sixteen cases of acute kidney injury resulting from synthetic cannabinoid abuse have been reported.[49] JWH-018 has also been associated with strokes in two healthy adults.[50]

It should be noted that pre-mixed, branded blends (like Spice and K2) are more dangerous than pure powder because the specific chemicals and dosages are usually unlisted as well as the potential of inconsistent areas of dense powder, leading to an overdose. As synthetic cannabinoids are active in the milligram range (with below 5mg being a common dose), it is important to use proper precautions when dosing to avoid a negative experience.

Like THC, prolonged usage of synthetic cannabinoids may increase one's disposition to mental illness and psychosis[42], particularly in vulnerable individuals with risk factors for psychotic illnesses (like a past or family history of schizophrenia).[51][52][36] It is recommended that individuals with risk factors for psychotic disorders not use synthetic cannabinoids.[53]

Although there is no valid data on the toxicity of synthetic cannabinoids so far, there is concern that the naphthalene group found in THJ-018 and some other synthetic cannabinoids may be toxic or carcinogenic.[54][55][56][57]

It is strongly recommended that one use harm reduction practices when using these drugs.

Common substances

Brand-name mystery blends

Comparison of synthetic cannabinoids

Please be aware that pre-mixed, branded blends are unreliable as they often fail to list the constituents and dosages. Many people have been hospitalised or suffered negative symptoms believing they are comparable to cannabis in potency and effects. This is not the case, and they should be avoided in favour of pure analytical samples where possible.

Indazolecarboxamides

Indolecarboxamides

Indolecarboxylates

Naphthoylindoles

Naphthoylindazoles

Tetramethylcyclopropanoylindoles

Comprehensive List

For a comprehensive list of known synthetic cannabinoid derivatives, /r/Drugs/wiki has published a respectable directory of names and links to further information.

External links

References

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  2. 2.0 2.1 Lambert, D. M., Fowler, C. J. (11 August 2005). "The endocannabinoid system: drug targets, lead compounds, and potential therapeutic applications". Journal of Medicinal Chemistry. 48 (16): 5059–5087. doi:10.1021/jm058183t. ISSN 0022-2623. 
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