Does CBN help with insomnia?

CBN or cannabinol is a non-enzymatic oxidative by-product of THC.

It has a lower affinity for CB1 and CB2 receptors compared to THC (10% of the activity of Δ9-THC at the CB1 receptors).

CBN has been promoted to assist patients that are suffering from insomnia but this claim has not been substantiated by any clinical trials.

Research by Musty et al., reported that oral ingestion of 50 mg CBN did not induce dizziness or drowsiness in human subjects.

“It appears that CBN increases the effect of delta9-THC on some aspects of physiological and psychological processes, but that these effects are small and cannot account for the greater potency which has been reported when plant material is used”.

As the result of the low affinity of CBN to cannabinoid receptors and limited available evidence, CBN shall not be claimed to be a sedative.

Adequate clinical trials focused specifically on the sedative effects of CBN are required to further evaluate potential other mechanisms that may be responsible for reported anecdotal claims by users.

References:

  1. Health Canada. (2018). Information for Health Care Professionals: Cannabis (marihuana, marijuana) and the cannabinoids. Ottawa: Health Canada.
  2. Merzouki A, Mesa JM. Concerning kif, a Cannabis sativa L. preparation smoked in the Rif mountains of northern Morocco. J Ethnopharmacol. 2002;81(3):403-406. doi:10.1016/s0378-8741(02)00119-8.
  3. Pertwee RG. The diverse CB1 and CB2 receptor pharmacology of three plant cannabinoids: Delta9-tetrahydrocannabinol, cannabidiol and delta9-tetrahydrocannabivarin. Br J Pharmacol 2008 01;153(0007-1188; 0007-1188; 2):199-215.
  4. Izzo AA, Borrelli F, Capasso R, Di M,V, Mechoulam R. Non-psychotropic plant cannabinoids: New therapeutic opportunities from an ancient herb. Trends Pharmacol Sci 2009 10;30(1873-3735; 0165-6147; 10):515-27.
  5. Evans FJ. Cannabinoids: the separation of central from peripheral effects on a structural basis. Planta Med. 1991;57:S60–S67.
  6. Musty RE, Karniol IG, Shirikawa I, Takahashi RN, Knobel E. Interactions of delta-9-tetrahydrocannabinol and cannabinol in man. In: Braude MC, Szara S, editors. The Pharmacology of Marihuana. Vol. 2. New York: Raven Press; 1976. pp. 559–563.

THCA and its potential pharmacological effects

THCA is generally referred to as an inactive precursor of THC, but research has demonstrated that this chemical compound may have potential therapeutic properties.

Δ9‐THCA is produced naturally in the cannabis plant. It is a non‐psychotropic cannabinoid and its potential to bind to CB1 receptors is still debated.

A more recent study by McPartland et.al. showed that freshly prepared and highly pure Δ9‐THCA (98%) has a low binding affinity for CB1 and CB2 receptors1.

THCA-A has shown to inhibit the release of TNFα in a dose-dependent manner and, weakly inhibit cyclooxygenase enzymes (COX-1 and COX-2) in a high concentration range (mM), compared with nonsteroidal anti-inflammatory medications (NSAIDs)2.

The anti-inflammatory activity of Cannabis extracts on colon epithelial cells of an IBD model is suggested to be derived from THCA3. This study suggested that the anti-inflammatory activity of THCA was at least partially mediated by GPR55 receptor agonism.

It is suggested that Δ9‐THCA enters the CNS and PPARγ is the major target responsible for its neuroprotective and anti‐inflammatory activity4&5. THCA-A binds and activates PPARγ with higher potency than THC5.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5731255/figure/bph14019-fig-0001/

Δ9-THCA-A is a partial and selective PPARγ modulator, empowered with lower adipogenic activity than the full PPARγ agonist rosiglitazone (RGZ) and enhanced osteoclastogenic effects in hMSC4. It is proposed that Δ9-THCA-A as a low adipogenic PPARγ agonist, may be capable of improving the symptoms of obesity-associated metabolic syndrome and inflammation4.

Δ9‐THCA has been shown to be neuroprotective in mice treated with 3‐NPA, improving motor deficits and preventing striatal degeneration. It attenuates microgliosis, astrogliosis, and up‐regulation of pro-inflammatory markers induced by 3‐NPA in mice5.

Δ9‐THCA shows potent neuroprotective activity, which warrants its consideration for the investigation of treatments of Huntington’s disease and other neurodegenerative and neuroinflammatory conditions.

REFERENCES:

  1. McPartland JM, McDonald C, Young M, Grant Phillip S, Furkert DP, Glass M (2017). Affinity and efficacy studies of tetrahydrocannabinolic acid A at cannabinoid receptor types one and two. Cannabis Cannabinoid Res 2: 87–95.
  2. Ruhaak LR, Felth J, Karlsson PC, et al. Evaluation of the cyclooxygenase inhibiting effects of six major cannabinoids isolated from Cannabis sativa. Biol Pharm Bull. 2011;34:774–778.
  3. Nallathambi R, Mazuz M, Ion A, et al. Anti-Inflammatory Activity in Colon Models Is Derived from Δ9-Tetrahydrocannabinolic Acid That Interacts with Additional Compounds in Cannabis Extracts. Cannabis Cannabinoid Res. 2017;2(1):167–182. Published 2017 Jul 1. doi:10.1089/can.2017.0027.
  4. Palomares B, Ruiz-Pino F, Garrido-Rodriguez M, et al. Tetrahydrocannabinolic acid A (THCA-A) reduces adiposity and prevents metabolic disease caused by diet-induced obesity. Biochem Pharmacol. 2020;171:113693. doi:10.1016/j.bcp.2019.113693.
  5. Nadal X, Del Río C, Casano S, et al. Tetrahydrocannabinolic acid is a potent PPARγ agonist with neuroprotective activity. Br J Pharmacol. 2017;174(23):4263–4276. doi:10.1111/bph.14019.

Cannabis strains used in research in the US are more similar to hemp

Can we generalize the result of clinical studies to patients’ experience?

The genetics of cannabis strains used in research in the US is different from commercially available products. Therefore, the clinical effect of the studied strains may be different from the patient-reported outcomes.

According to a recent study analyzed the genetics of 49 cannabis strains from different sources including NIDA (National Institute on Drug Abuse) and dispensaries in Colorado, California, and Washington. The researchers found that strains can be grouped into two major categories: drug-type strains and hemp-like strains and the genome of both strains sourced from NIDA looks like hemp. Dr. Anna Schwabe, one of the authors of the study says that “I personally don’t think they’re providing something that’s similar to what any patient could get their hands on,”.

It worth noting that all scientists in the US have to get their cannabis strains for research purposes from DEA & NIDA approved sources. The only licensed source is currently the National Center for Natural Products Research at the University of Mississippi.

You can find the excerpt of the study in Nature and the original study here.

Manipulation of the endocannabinoid system could be a promising therapy to control Parkinson’s disease and l-DOPA-induced dyskinesia symptoms

According to a literature review published in the journal of Neurotoxicity Research, cannabinoids, provide a potential multi-targeted treatment strategy for patients with Parkinson’s disease and dyskinesia.

Picture Source : WebMD/3D4 Medical

https://link.springer.com/article/10.1007%2Fs12640-019-00109-8