Use of CBD in the treatment of anxiety

Use of CBD in the treatment of anxiety

What is anxiety?

As opposed to fear, which is the emotional response to an immediate threat, anxiety can be defined as the apprehension of a future threat or possible outcome. [1,2] Anxiety is a normal emotion that has been an asset from an evolutionary perspective. The survival instincts of both humans and animals can be attributed wholly to this emotion. [1]

Owing to the sensory overload, deprived sleep patterns and erratic work schedule that has become an everyday affair in the modern world, anxiety and stress is on an all-time high.

What is an anxiety disorder?

The differentiating factor between anxiety and medically diagnosed anxiety disorder is clinical judgement in terms of triggers, frequency of triggers, the intensity of response, physical symptoms, etc.

The physical/mental/emotional response to a situation can be rendered out of proportion and unmanageable to the extent that the daily functioning of the individual is hampered. [3]

Types of Anxiety Disorders

Anxiety disorder can be further categorized based on the symptoms, the majority of which are:

  • Generalized Anxiety Disorder (GAD)- Characterized by underlying chronic anxiety and excessive worrying even in a normal situation i.e. absence of ordinary triggers.[4]
  • Obsessive Compulsive Disorder (OCD) – Characterized by recurrent thoughts i.e. obsessions and repetitive acts/rituals and patterns i.e. compulsions in response to the triggers.[4]
  • Panic Disorder- Characterized by the intense physical symptoms associating with anxiety not limited to heart palpitations, shortness of breath, gastrointestinal distress, chest pain and dizziness.[4]
  • Post-Traumatic Stress Disorder (PTSD)- Anxiety Disorder in response to a remarkably grave and traumatic incident that can be invoked in response to any instance that is remotely linked to the incident. [4]
  • Social Anxiety Disorder- characterized by overwhelming self-consciousness in daily social interactions and anxiety piping through conversations. Fear of public speaking or nervousness related to eating/drinking in front of others or excessive worrying prior to a social event. [4]

 

CBD in the Mental Health Scenario:

CBD or Cannabidiol should not be confused with marijuana; CBD is extracted from hemp i.e. Cannabis Sativa with THC concentration less than 0.3%. [5]

Cannabis sativa belongs to the Cannabaceae family with a low concentration of delta-9-tetrahydrocannabinol (THC) i.e. the main psychoactive component which produces relaxation, mild euphoria, sedation, and perceptual distortion. [6,7]

The other major Phyto-cannabinoid component CBD promises a wide range of therapeutic properties, including antipsychotic, analgesic, neuroprotective, anticonvulsant, antiemetic, antioxidant, anti-inflammatory, antiarthritic and antineoplastic properties but lacks the psychoactive properties of THC. [7]

 

Anxiolytic effect of CBD

Anxiolytics (also termed anti-anxiety or anti-panic drugs) are a group of medications/ interventions that are used to treat anxiety disorders and the associated psychological and physical symptoms. [8]

The Cannabis sativa constituent- CBD is a pharmacologically broad-spectrum drug showcases evidence from human studies that supports an anxiolytic role of CBD when administered acutely. [7]

The preclinical evidence supports CBD as a treatment for multiple anxiety disorders: generalized anxiety disorder, panic disorder, social anxiety disorder, obsessive–compulsive disorder, and post-traumatic stress disorder but only with acute dosage. [7]

Let us take a further dive into evidence and studies on the role of CBD in the market of anxiolytics.

CBD exhibits a broad range of actions including anxiolytic (property associated with reduced anxiety), panicolytic (property associated with reduced fight reflex mechanism in the body while sensing stress/danger), and anti-compulsive actions (reducing the impulsive and overpowering need to perform repetitive actions associated with OCD), decrease in autonomic arousal and conditioned fear expression, enhancement of fear extinction, reconsolidation blockade, and prevention of the long-term anxiogenic (opp. of anxiolytic) effects of stress. [7] 

The animal models have been studied extensively when it comes to the anxiolytic properties of CBD, though species discrepancies are apparent. [7]. CBD has been studied in a wide range of animal models of general anxiety, including the elevated plus maze (EPM), the Vogel-conflict test (VCT), and the elevated T maze (ETM). 

For a deeper understanding of the studies conducted on animal models, please refer to the links – [7, 9-39]

Evidence from human studies suggests the potential for CBD as a treatment for anxiety disorders at an oral dosage ranging from 300 to 600 mg reducing experimentally induced anxiety in healthy controls, without affecting baseline anxiety levels and reduces anxiety in patients with SAD. Limited results in healthy subjects also support the efficacy of CBD in acutely reducing fear levels indicating the potential for the treatment for PTSD and enhancing cognitive behavioral therapy.[7] 

 

Safety and Dosage

Studies indicate that CBD is non-toxic in non-transformed cells and does not induce changes in food intake or induce catalepsy, does not affect physiological parameters and gastrointestinal transit, nor does it alter psychomotor or psychological functions. [42]

Chronic usage and high doses up to 1500 mg per day are shown to be well tolerated in humans. [40,41,42] CBD injected through different routes and long-term use of 10 mg/d to 400 mg/d did not create a toxic effect on patients.  [42]

CBD was shown to be helpful for decreasing anxiety through an experimentally simulated public speaking scenario at doses of 300 mg to 600 mg in acute dosage studies. [43-45]  

Results are consonant with evidence from preclinical studies and support the view that CBD induces acute anxiolytic effects with an inverted U-shaped dose-response curve in humans. 

60 volunteers were randomly allocated to five groups with 12 subjects each to receive different doses of CBD (100, 300, and 900 mg), clonazepam (1 mg) (Clonazepam being one of the most common pharmaceutical anxiolytics for the treatment of various anxiety disorders whose safety profile is superior to the other benzodiazepines[46]) or placebo in a double-blind, randomized design. [43]

The below figure shows the comparison of anxiety levels in each of the five groups 

Figure 1

 

comparison of anxiety levels

 

Key Takeaways:

  1. CBD has the potential for a breakthrough in the mental health landscape.
  2. CBD has an undeniable anxiolytic effect when administered acutely
  3. Consumption of CBD even at higher doses of 1500 mg per day is well tolerated by healthy individuals.
  4. CBD shows an inverted U-shaped dose-response curve in humans with acute dosing.
  5. Most of the research done has been in animal models and have shown promising results.
  6. Further research is needed to study the effects of CBD with chronic consumption.
  7. There is a definite need for randomized controlled experiments with human subjects having preexisting anxiety disorders.

 

References:

  1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4610616/#ref1
  2. https://scholar.google.com/scholar_lookup?journal=Diagnostic+and+Statistical+Manual+of+Mental+Disorders.+5th+ed.+Arlington,+VA:+American+Psychiatric+Association;&title=American+Psychiatric+Association:&publication_year=2013&
  3. https://www.psychiatry.org/patients-families/anxiety-disorders/what-are-anxiety-disorders
  4. https://www.hhs.gov/answers/mental-health-and-substance-abuse/what-are-the-five-major-types-of-anxiety-disorders/index.html
  5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6140266/
  6. https://www.sciencedirect.com/topics/agricultural-and-biological-sciences/cannabis-sativa
  7. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4604171/#:~:text=The%20anxiolytic%20effects%20of%20CBD,alone%20%5B99%2C%20100%5D.
  8. https://www.medicinenet.com/anxiolytics_for_anxiety_drug_class/article.htm
  9. https://scholar.google.com/scholar_lookup?journal=Res+Commun+Psychol+Psychiatry+Behav&title=Comparative+effects+between+cannabidiol+and+diazepam+on+neophobia,+food+intake+and+conflict+behavior&author=NG+Silveira+Filho&author=S+Tufik&volume=6&publication_year=1981&pages=25-26&
  10. https://scholar.google.com/scholar_lookup?journal=Arch+Int+Pharmacodyn+Ther&title=Characteristics+of+the+stimulus+produced+by+the+mixture+of+cannabidiol+with+delta+9-tetrahydrocannabinol&author=AW+Zuardi&author=E+Finkelfarb&author=OF+Bueno&author=RE+Musty&author=IG+Karniol&volume=249&publication_year=1981&pages=137-146&pmid=6261703&
  11. https://www.ncbi.nlm.nih.gov/pubmed/2162942
  12. https://www.ncbi.nlm.nih.gov/pubmed/16876926
  13. https://www.ncbi.nlm.nih.gov/pubmed/16780966
  14. https://www.ncbi.nlm.nih.gov/pubmed/18446323
  15. https://scholar.google.com/scholar_lookup?journal=Eur+Neuropsychopharmacol&title=Facilitation+of+contextual+fear+memory+extinction+and+anti-anxiogenic+effects+of+AM404+and+cannabidiol+in+conditioned+rats&author=RM+Bitencourt&author=FA+Pamplona&author=RN+Takahashi&volume=18&publication_year=2009&pages=849-859&pmid=18706790&doi=10.1016/j.euroneuro.2008.07.001&
  16. https://www.ncbi.nlm.nih.gov/pubmed/19735690
  17. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2697769/
  18. https://scholar.google.com/scholar_lookup?journal=Behav+Brain+Res&title=Intra-dorsal+periaqueductal+gray+administration+of+cannabidiol+blocks+panic-like+response+by+activating+5-HT1A+receptors&author=P+Soares+Vde&author=AC+Campos&author=VC+Bortoli&volume=213&publication_year=2010&pages=225-229&pmid=20457188&doi=10.1016/j.bbr.2010.05.004&
  19. https://www.ncbi.nlm.nih.gov/pubmed/19785914
  20. https://www.ncbi.nlm.nih.gov/pubmed/19800921
  21. https://www.ncbi.nlm.nih.gov/pubmed/20695034
  22. https://www.ncbi.nlm.nih.gov/pubmed/20945065
  23. https://www.ncbi.nlm.nih.gov/pubmed/21771609
  24. https://scholar.google.com/scholar_lookup?journal=Psychopharmacology+(Berl)&title=Plasma+and+brain+pharmacokinetic+profile+of+cannabidiol+(CBD),+cannabidivarine+(CBDV),+Delta(9)-tetrahydrocannabivarin+(THCV)+and+cannabigerol+(CBG)+in+rats+and+mice+following+oral+and+intraperitoneal+administration+and+CBD+action+on+obsessive-compulsive+behaviour&author=S+Deiana&author=A+Watanabe&author=Y+Yamasaki&volume=219&publication_year=2012&pages=859-873&pmid=21796370&doi=10.1007/s00213-011-2415-0&
  25. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3242302/
  26. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3398715/
  27. https://www.ncbi.nlm.nih.gov/pubmed/22979992
  28. https://www.ncbi.nlm.nih.gov/pubmed/21867717
  29. https://www.ncbi.nlm.nih.gov/pubmed/21148020
  30. https://www.ncbi.nlm.nih.gov/pubmed/22083592
  31. https://www.ncbi.nlm.nih.gov/pubmed/23298518
  32. https://www.ncbi.nlm.nih.gov/pubmed/23643693
  33. https://www.ncbi.nlm.nih.gov/pubmed/23007604
  34. https://www.ncbi.nlm.nih.gov/pubmed/23127569
  35. https://www.ncbi.nlm.nih.gov/pubmed/23041353
  36. https://www.ncbi.nlm.nih.gov/pubmed/23926240
  37. https://www.ncbi.nlm.nih.gov/pubmed/24321837
  38. https://www.ncbi.nlm.nih.gov/pubmed/24118015
  39. https://www.ncbi.nlm.nih.gov/pubmed/25841876
  40. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6326553/
  41. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5569602/
  42. https://pubmed.ncbi.nlm.nih.gov/22129319/
  43. https://www.ncbi.nlm.nih.gov/pubmed/28553229/
  44. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3079847/
  45. https://www.ncbi.nlm.nih.gov/pubmed/22290374
  46. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4857865/

 

Leave a Comment

Your email address will not be published. Required fields are marked *