Marijuana (Cannabis)

THCA (Tetrahydrocannabinolic Acid)

by Jermane Krshnan

Tetrahydrocannabinolic acid (THCA or 2-COOH-THC) is a precursor of tetrahydrocannabinol (Δ-9 THC), the major active component of cannabis. THCA is gaining attention as more is learned about its therapeutic benefits, especially its analgesic and anti-inflammatory properties.


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See also: ∆-9 THC


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Definitions and Terms Related to Pain


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Botanical Cannabis and the Cannabinoid Acids

The most abundant of the cannabinoids are Δ-9 THC (tetrahydrocannabinol) and CBD (cannabidiol). Only the Δ-8 THC, Δ-9 THC, and their hydroxyl metabolites are psychoactive. Mosy of the therapeutic benefits from marijuana come from Δ-9 THC and CBD.


Cannabinoids are synthesized and stored predominantly in glandular trichomes, hair-like epidermal protrusions densely concentrated in the flowers of cannabis plants.


Botanical cannabis is highly variable in its chemical composition and content of the cannabinoids THC and CBD. Fresh cannabis plants in actuality contain little to no THC and CBD but instead contain tetrahydrocannabinolic acid (THCA) and cannabadiolic acid (CBDA), the precursors or pro-drugs to THC and CBD respectively. These acid cannabinoids have had much less research, but are known to possess pharmacological properties in their own right. 


Cannabinoid acids  in raw and live cannabis 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.



Tetrahydrocannabinolic Acid (THCA)

Tetrahydrocannabinolic acid (THCA or 2-COOH-THC) is a precursor of tetrahydrocannabinol (THC), the major 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, although slow decarboxylation of ∆9-THC occurs at room temperature.



More than 90% of the THC in cannabis plants grown in Europe is present as THCA, while cannabis grown in hot climates of Africa and Asia contain considerable more THC. The ratio of ∆9-THCA to ∆9-THC in leaves and flowers of Cannabis sativa has been reported to range from 2:1 in Africa to > 20:1 in Switzerland. In samples of cannabis resin (hashish) the THCA/THC ratio is reported to range between 6.1:1 and 0.5:1.



For THCA to become activated and converted to THC for therapeutic use, it generally must be exposed to intense heat such as when cannabis is smoked or cooked into cannabis edibles. THCA is often the main constituent in cannabis resin concentrates, such as hashish and hash oil comprising 50% – 90% by weight.


It has been reported that five minutes of heating to 200-210°C is optimal for this conversion, a few seconds in a burning cannabis cigarette is sufficient. Cannabis products with a high content of ∆9-THC (e.g., hashish) may be very potent without heating, but usually the potency and medicinal efficacy of cannabis products is significantly increased with smoking the dried plant matter, or by cooking and baking.


THCA ‘s potential benefits include reducing inflammation associated with arthritis and autoimmune diseases. It may also help reduce symptoms of neurological conditions such as Parkinson’s disease and amyotrophic lateral sclerosis (ALS).


THCA is not psychoactive like THC but does have some immuno-modulating effects but they are not mediated by the cannabinoid CB1 and CB2 receptor pathways. THCA is a TRPA1 partial agonist, and a TRPM8 antagonist which may underlie a potential role in the analgesia, and anti-inflammatory and anti-nausea properties.Tetrahydrocannabinol acid (THCA) is similar to THC, but it doesn’t cause any psychoactive effects.



Neurobiology of THCA

As peer a 2020 study, ∆9-THCA is a partially agonist of CB1 receptor (CB1R) and CB2 receptor (CB2R), with greater affinity for CB2 receptor.  ∆9-THCA produces analgesic and hypolocomotive effects and anxiolytic-like effects.   ∆9-THCA binding to CB1R and CB2R, with potential orthosteric and allosteric activity at CB1R. The anti-inflammatory activity of ∆9-THCA in a rodent model of arthritis is CB1R- and peroxisome proliferator-activated receptor γ (PPARγ)-dependent.

The analgesic effect of ∆9-THCA is likely in part due to CB1R agonism. Studies, indicate ∆9-THCA may mediate neuroprotective and anti-inflammatory actions via CB1R, CB2R, and PPARγ when administered at sufficiently high concentrations and in the absence of other cannabinoids.




National Academy of Sciences

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

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




Terpenes – Overviews:

  1. Taming THC – potential cannabis synergy 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
  25. Cannabis Use in Patients with Fibromyalgia – Effect on Symptoms Relief and Health-Related Quality of Life – 2011
  26. Weighing the Benefits and Risks of Medical Marijuana Use – A Brief Review – 2018
  27. A Marijuana-Drug Interaction Primer – Precipitants, Pharmacology, and Pharmacokinetics – 2019
  28. Myorelaxant Effect of Transdermal Cannabidiol Application in Patients with TMD – A Randomized, Double-Blind Trial – 2019
  29. Drug interactions with cannabinoids – 2020
  30. The effects of acute and sustained cannabidiol dosing for seven days on the haemodynamics in healthy men – A randomised controlled trial – 2019
  31. Novel approaches and current challenges with targeting the endocannabinoid system – 2020
  32. Herbal Preparations of Medical Cannabis – A Vademecum for Prescribing Doctors – 2020
  33. Cannabis is associated with clinical but not endoscopic remission in ulcerative colitis – A randomized controlled trial – 2020
  34. Practical Strategies Using Medical Cannabis to Reduce Harms Associated With Long Term Opioid Use in Chronic Pain – 2021
  35. Endocannabinoid Levels in Ulcerative Colitis Patients Correlate With Clinical Parameters and Are Affected by Cannabis Consumption – 2021
  36. The pharmacokinetics and the pharmacodynamics of cannabinoids – 2018


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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