Cannabinoids

 

 

See:

Marijuana – Legislative Update

Marijuana – Medical Use Overview

Marijuana – Prescription Cannabinoids

Marijuana – Cannabidiol (CBD)

Marijuana – Edibles (coming soon)

Marijuana – Inhaled (Smoked and Vaporized)

Marijuana – Cannabinoids and Opioids (coming soon)

Marijuana – Pharmacokinetics

Marijuana – The Endocannabinoid System (coming soon)

    

See also:

Marijuana – Discontinuing Use

Marijuana Addiction – Cannabis Use Disorder (CUD)

 

 

Key to Links:

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The medical information on this site is provided as a resource for information only, and is not to be used or relied upon for any diagnostic or treatment purposes and is not intended to create any patient-physician relationship.  Readers are advised to seek professional guidance regarding the diagnosis and treatment of their medical concerns.

 

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Cannabiniods

What are Cannabiniods?

Cannabiniods are organic chemical compounds (alkaloids) found in cannabis plants. More than 600 compounds have been identified in cannabis, but only the cannabinoids Δ-8 THC, Δ-9 THC, and their hydroxyl metabolites  are psychoactive. The clinical benefits from marijuana are derived from the many constituents found in the plant, including more than 100 pharmacologically active constituents, including cannabinoids and terpenes. The two best understood and most common of the cannabinoids are Δ-9 THC (tetrahydrocannabinol) and CBD (cannabidiol).

 

Cannabinoid Acids

Cannabinoid acids are the precursors to the cannabinoids in raw and live cannabis, and have no psychotropic qualities. They are decarboxylated by heat, UV exposure, and prolonged storage to form the active cannabinoids, although heat such as from smoking or vaporizing is the primary conversion factor.  Cannabinoid acids are gaining attention as more is learned about their therapeutic benefits, especially their analgesic and anti-inflammatory properties.

 Δ-9 THC (Tetrahydrocannabinol)

THC has analgesic, anti-spasmodic, anti-tremor, anti-inflammatory, appetite stimulant and anti-emetic properties, whilst CBD is non-euphoric but has anti-anxiety, anti-depressant, anti-inflammatory, anti-convulsant, anti-psychotic, anti-oxidant, neuroprotective and immunomodulatory effects. CBD is a versatile anti-inflammatory analgesic through numerous distinct mechanisms.

The clinical benefits from marijuana are derived from the many constituents found in the plant, including more than 80 pharmacologically active cannabinoids. The two best understood and most common of these cannabinoids are THC (tetrahydrocannabinol) and CBD (cannabidiol). There is very limited scientific information on the pharmacology and toxicology of the other cannabinoids and pharmacologially active constituents found in cannabis.

With respect to the management of pain, studies suggest that THC alone may not be sufficient for a good analgesic effect. This means that THC may need to be combined with CBD in order to achieve good results. THC is responsible for many of the clinical effects of marijuana, including the analgesic, anti-spasmodic, anti-tremor, anti-inflammatory, appetite stimulant and anti-emetic properties.  THC and its active metabolite, 11-Hydroxy-THC. are responsible for the “high” or euphoria associated with use of marijuana.

See: THC (tetrahydrocannabinol)

   

Tetrahydrocannabinolic Acid (THCA)

Tetrahydrocannabinolic acid (THCA or 2-COOH-THC) is a precursor of tetrahydrocannabinol (THC), the active component of cannabis. THCA is found in variable quantities in fresh, undried cannabis, but is progressively decarboxylated and converted to THC with drying or with exposure to intense heat such as when cannabis is smoked or cooked. THCA is often the majority constituent in cannabis resin concentrates, such as hashish and hash oil comprising
50% – 90% by weight. THCA is a TRPA1 partial agonist, and TRPM8 antagonist which may underlie a potential role in analgesia, and has been shown to have anti-inflammatory and anti-nausea properties.

 

CBD (Cannabidiol)

CBD does not produce the mind-altering “high” effects like euphoria but it does reduce anxiety and enhance sleep. It has anti-inflammatory, anti-convulsant, anti-psychotic, anti-oxidant, neuroprotective and immunomodulatory effects. CBD is also thought to reduce nausea, particularly related to chemotherapy. CBD, in combination with THC, modulates some of the side effects of THC, including reducing THC-induced anxiety.

See: CBD (Cannabidiol)

 

CBDA (Cannabidiolic acid)

Cannabidiolic acid (CBDA) is a phytocannabinoid found in raw cannabis, meaning fresh flowers and leaves that are unheated. CBDA is decarboxylated to CBD with heat and light exposure. CBDA is often ingested through consumption of raw cannabis juice. It is a TRPA1 agonist, TRPV1 agonist, and TRPM8 antagonist which may also reflect its potential as an analgesic. It is also anti-inflammatory via selective COX2 inhibition, and has anti-nausea properties.

CBN (Cannabinol)

The third most common constituent of marijuana is cannabinol (CBN). Cannabinol (CBN) is a non-psychoactive cannabinoid found in fresh cannabis plant, usually in low amounts.  Unlike other cannabinoids, CBN does not stem from cannabigerol (CBG) but is the nonenzymatic oxidative breakdown product of tetrahydrocannabinol (THC), seen in aged cannabis, and has about 25% of the potency of THC. In the evaluation of the freshness of a dried cannabis product levels of CBN, coupled with levels of THCA can potentially identify if the cannabis product has been stored properly. CBN is also formed by decarboxylation of CBNA.  but it is not yet (?) commercially available as an isolated compound.

 

CBN likely plays a small role in the pharmacologic effects of plant based cannabis products, but does show similar therapeutic properties to other phytocannabinoids, including pain relief as well as anticonvulsant, anti-inflammatory, and antibacterial activity. It inhibits transient receptor potential melastatin 8 (TRPM8) channels and it inhibits cyclooxygenase (COX).

 

CBG (Cannabigerol)

Cannabigerol (CBG) is a non-psychoactive cannabinoid found in the fresh cannabis plant. CBG is made by the decarboxylation of cannabigerolic acid (CBGA). CBG is a highly potent agonist for α2 adrenoceptor and a blocker of serotonin 5-HT1A receptor. This activity can decrease anxiety and muscle tension. CBG is notable among all other cannabinoids as being the precursor to each one of them, lending to its nickname: “The Mother All Cannabinoids.” In particular, it has a direct link to the three most significant and abundant cannabinoids: THC, CBD and CBC. Therefore, the more THC a cannabis plant contains, the less CBG and vice-versa.

 

CBG shows agonist and antagonist activity on TRP channels and antagonism at 5-HT1 and CB1 receptor. Additionally, CBG is an AEA reuptake inhibitor, and it showed colon anti-tumor activity by inhibiting transient receptor potential melastatin 8 (TRPM8) channels. When associated with CBD, it has anti-inflammatory activity by reducing tumor necrosis factor (TNF) expression and upregulating Interleukin–10 (IL-10) and Interleukin–37 (IL-37) levels.

 

Cannabigerol Acid (CBGA)

 

CBDV (Cannabidivarin)

Cannabidivarin (CBDV) is a non-psychoactive cannabinoid known for its anticonvulsant effects. CBDV and cannabidiol (CBD) activate and desensitize transient receptor potential vanilloid 1 (TRPV1) channels in vitro.

 

Cannabidivarin Acid (CBDVA)

 

Cannabichromene (CBC)

Cannabichromene (CBC) is a CB2 receptor agonist and it interacts with TRP channels. It has potential for the treatment of pain and inflammation.

Cannabichromene Acid (CBCA)

 

Delta 8 Tetrahydrocannabinol (Δ8THC)

 

Tetrahydrocannabivarin (THCV)

THCV appears to activate the 5-HT1A receptor which accounts for its apparent antipsychotic effects, reducing some of the symptoms of schizophrenia.

 

 

Resources:

National Academy of Sciences

The Health Effects of Cannabis and Cannabinoids: The Current State of Evidence and Recommendations for Research

 

www.Healer.com

This website appears to be good resource for exploring medical marijuana.

 

References:

   

Terpenes – Overviews:

  1. Taming THC – potential cannabis sy
    nergy and
    phytocannabinoid-terpenoid entourage effects – 2011
  2. A tale of two cannabinoids: the therapeutic rationale for combining tetrahydrocannabinol and cannabidiol. – PubMed – NCBI
  3. Human Pharmacokinetic Parameters of Orally Administered Δ 9-Tetrahydrocannabinol Capsules Are Altered by Fed Versus Fasted Conditions and Sex Differences – PubMed
  4. Medicinal Properties of Cannabinoids, Terpenes, and Flavonoids in Cannabis, and Benefits in Migraine, Headache, and Pain – An Update on Current Evidence and Cannabis Science – 2018

Cannabinoids: Caryophyllene:

  1. (−)-β-Caryophyllene, a CB2 Receptor-Selective Phytocannabinoid, Suppresses Motor Paralysis and Neuroinflammation in a Murine Model of Multiple Sclerosis – 2017
  2. Antiallodynic effect of β-caryophyllene on paclitaxel-induced peripheral neuropathy in mice. – PubMed – NCBI

 

CBD – Anxiety

  1. Overlapping Mechanisms of Stress-Induced Relapse to Opioid Use Disorder and Chronic Pain – Clinical Implications – 2016
  2. Cannabidiol Modulates Fear Memory Formation Through Interactions with Serotonergic Transmission in the Mesolimbic System – 2016
  3. Cannabidiol regulation of emotion and emotional memory processing: relevance for treating anxiety-related and substance abuse disorders. – PubMed – NCBI
  4. Review of the neurological benefits of phytocannabinoids – 2018
  5. Plastic and Neuroprotective Mechanisms Involved in the Therapeutic Effects of Cannabidiol in Psychiatric Disorders – 2017
  6. Neural basis of anxiolytic effects of cannabidiol (CBD) in generalized social anxiety disorder: a preliminary report. – PubMed – NCBI
  7. Evidences for the Anti-panic Actions of Cannabidiol – 2017
  8. Cannabidiol, a Cannabis sativa constituent, as an anxiolytic drug – 2012
  9. Cannabidiol Reduces the Anxiety Induced by Simulated Public Speaking in Treatment-Naïve Social Phobia Patients – 2011

 

Cannabinoids – Pain

  1. Association of Cannabinoid Administration With Experimental Pain in Healthy Adults – 2018
  2. Effects of Cannabinoid Administration for Pain – A Meta-Analysis and Meta-Regression – 2019
  3. Cannabis-based medicines and the perioperative physician – 2019
  4. Cannabis‐based medicines for chronic neuropathic pain in adults – 2018
  5. Cannabinoids in the Descending Pain Modulatory Circuit- Role in Inflammation – 2020
  6. Current Evidence of Cannabinoid-Based Analgesia Obtained in Preclinical and Human Experimental Settings – PubMed – 2018
  7. Role of Cannabinoids and Terpenes in Cannabis-Mediated Analgesia in Rats – PubMed – 2019
  8. Medicinal Properties of Cannabinoids, Terpenes, and Flavonoids in Cannabis, and Benefits in Migraine, Headache, and Pain – An Update on Current Evidence and Cannabis Science – 2018
  9. The Molecular Mechanisms That Underpin the Biological Benefits of Full-Spectrum Cannabis Extract in the Treatment of Neuropathic Pain and Inflammation – PubMed – 2020
  10. Cannabis sativa L. an
    d Nonpsychoactive Cannabinoids – Their Chemistry and Role against Oxidative Stress, Inflammation, and Cancer – 2018
  11. Cannabinoid Delivery Systems for Pain and Inflammation Treatment – 2018
  12. Cannabinoid Formulations and Delivery Systems – Current and Future Options to Treat Pain – 2021

 

CBD – Interaction with THC

  1. Cannabidiol: a promising drug for neurodegenerative disorders? – PubMed – NCBI
  2. Oral Cannabidiol does not Alter the Subjective, Reinforcing or Cardiovascular Effects of Smoked Cannabis – 2015
  3. Taming THC – potential cannabis synergy and phytocannabinoid-terpenoid entourage effects – 2011
  4. A tale of two cannabinoids: the therapeutic rationale for combining tetrahydrocannabinol and cannabidiol. – PubMed – NCBI

 

 

Cannabinoids: Tetrahydrocannabivarin (THCV):

  1. The phytocannabinoid, Δ9-tetrahydrocannabivarin, can act through 5-HT1A receptors to produce antipsychotic effects – 2015

 

Medical Marijuana –Misc

  1. A tale of two cannabinoids: the therapeutic rationale for combining tetrahydrocannabinol and cannabidiol. – PubMed – NCBI
  2. Cannabis and cannabis extracts – greater than the sum of their parts? – 2001
  3. Medical cannabis and mental health: A guided systematic review. 2016 – PubMed – NCBI
  4. Epidemiological characteristics, safety and efficacy of medical cannabis in the elderly. – PubMed – NCBI
  5. Cannabis-conclusions – 2017 National Academy of Sciences
  6. Cannabis-chapter-highlights – 2017 National Academy of Sciences
  7. Cannabis-report-highlights – 2017 National Academy of Sciences
  8. Clinical Endocannabinoid Deficiency (CECD): Can this Concept Explain Therapeutic Bene ts of Cannabis in Migraine, Fibromyalgia, Irritable Bowel Syndrome and other Treatment-Resistant Conditions?-2004
  9. Marijuana use and the risk of lung and upper aerodigestive tract cancers: results of a population-based case-control study. – PubMed – NCBI
  10. Cannabis use and cognitive function: 8-year trajectory in a young adult cohort. – PubMed – NCBI
  11. Cannabinoids for Medical Use: A Systematic Review and Meta-analysis. – PubMed – NCBI
  12. Cannabinoids and Cytochrome P450 Interactions. – PubMed – NCBI Pharmacogenetics of Cannabinoids – 2018
  13. Systematic review of systematic reviews for medical cannabinoids – 2018
  14. Adverse effects of medical cannabinoids – a systematic review – 2008
  15. Cannabimimetic effects modulated by cholinergic compounds. – PubMed – NCBI
  16. Antagonism of marihuana effects by indomethacin in humans. – PubMed – NCBI
  17. Pharmacokinetics and pharmacodynamics of cannabinoids. – PubMed – NCBI
  18. Clinical Pharmacodynamics of Cannabinoids – 2004
  19. Affinity and Efficacy Studies of Tetrahydrocannabinolic Acid A at Cannabinoid Receptor Types One and Two. – 2017
  20. Quality Control of Traditional Cannabis Tinctures – Pattern, Markers, and Stability – 2016
  21. Exogenous cannabinoids as substrates, inhibitors, and inducers of human drug metabolizing enzymes: a systematic review. – PubMed – NCBI
  22. Pharmacology of Cannabinoids
  23. Current-status-and-future-of-cannabis-research-Clin-Researcher-2015
  24. Medical Marijuana for Treatment of Chronic Pain and Other Medical and Psychiatric Problems – A Clinical Review – 2015

 

Medical Marijuana – Product Evaluation

  1. Recommended methods for the identification and analysis of cannabis and cannabis products – 2009
  2. The Cannabinoid Content of Legal Cannabis in Washington State Varies Systematically Across Testing Facilities and Popular Consumer Products – 2018
  3. Quality Control of Traditional Cannabis Tinctures – Pattern, Markers, and Stability – 2016
  4. Cannabinoid, Terpene, and Heavy Metal Analysis of 29 Over-the-Counter Commercial Veterinary Hemp Supplements – 2020

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