The regulation of anxiety, depression, PTSD, and bipolar disorders involve a wide array of chemical, neurological, and biological systems in the human body.  This regulation mainly involves components of the neurotransmitter system, and release and inhibition of certain chemicals involved in synaptic transmission, which affects the communication between nerve cells in the brain and nervous system. This in turn can affect and regulate mood, mental state and the feelings or perception of anxiety or depression.   In addition to neurochemical balance, psychological, social, and environmental conditions also play a role in the development and expression of anxiety and/or depression. A complex interplay of elements both physical and mental can lead to the development of alterations in an individual’s level of anxiety or depression. Both of these conditions are somewhat normal for individuals to experience at some point in their life, but when they become excessive and continuous the results can be debilitating.

 

     Usually the anxiety/depression diagnosis can be categorized into five general categories – Generalized Anxiety Disorder (GAD), Panic disorder, Social Anxiety Disorder, Obsessive Compulsive Disorder, and PTSD (post-traumatic stress disorder).

     

      A wide array of psychiatric drugs, in several different classes, are prescribed by physicians in order to help treat this disease and mitigate symptoms. These drugs include benzodiazepams, serotonin reuptake inhibitors, norepinephrine inhibitors, monoamine oxidase inhibitors, and others. They include the following – Celexa, Lexapro, Prozac, Paxil, Zoloft, Cymbalta, Effexor, Trintellix, Seroquel, Pristiq, Xanax, Wellbutrin, Abilify, Valium, among others.  It is important to note that psychological counseling, cognitive behavioral therapy, physical exertion and exercise, as well as other modes of therapy (yoga, meditation, mindfulness training, etc.…) can also help reduce symptoms. To best treat this disease a multifaceted and continuous approach using several modes of treatment is often needed.

 

      Some previous research concerning cannabis and anxiety has been focused on the two major endocannabinoids – Anandamide (arachidonylethanolamine) and 2-AG (2 arachidonylglycerol). These cannabinoids stimulate and bind to the CB1 and CB2 receptors located throughout your body to exert their effect... These two endocannabinoids are produced by the body as needed to maintain mental and physical wellness or homeostasis, and are similar in many respects to the phytocannabinoids found in the plant. They are part of the body’s endocannabinoid system, and they integrate and stimulate two cannabinoid receptors called CB1 and CB2, as well as other receptor systems. These g-protein coupled receptors are located on the cell walls of many cells, both in and out of the central nervous system, and can alter synaptic transmission of intracellular communications. The activation of these receptors from endocannabinoids or phytocannabinoids, may cause inhibition or promotion of intracellular signaling and neural transmission and affect your mood.  Your endocannabinoid system plays a direct role in emotions, anxiety, mental state, and feelings of well-being or depression, partially due to the cannabinoids interaction with the CB1 and CB2 receptors.

 

     Over the last several decades it has become apparent through clinical, anecdotal, and epidemiological data that the cannabis plant can regulate the symptoms of anxiety, using a similar mechanism as your own endocannabinoid system. Anxiolytic drugs REDUCE anxiety, and Anxiogenic drugs INCREASE anxiety. Keeping in mind the complexity of the cannabis plant (over 450 compounds), the main cannabinoids discussed in this article are THC and CBD, but other elements in the plant also play a role in altering your sense of anxiety or depression as well. One of these other cannabinoids useful in treating mood disorders is CBG, or Cannabigerol, and research is being done to examine its benefits for this disease. Other compounds would include terpenes, flavonoids, and a host of other cannabinoids as well as perhaps some yet undiscovered compounds. For the purpose of this article we will investigate THC and CBD, and also mention the endocannabinoids Anandamide and 2-AG. The endocannabinoids exert a similar effect as the phytocannabinoids on the CB1 and CB2 receptors, and both sets of cannabinoids can be useful for study and investigation.

 

      One of the major cannabinoids, THC (delta 9 tetrahydrocannabinol), has been reported to both reduce and/or also increase anxiety and depression in both animal and human models. This directly opposite reaction is documented in many studies, and also well-known anecdotally. Some patients respond adversely and have increased anxiety, whereas others will get a reduction in anxiety using cannabis. There is a large variation in response based on the patient’s biochemistry and individual metabolism, and the type of cannabis ingested. THC is responsible for most of the pharmacological effects in cannabis and can control or modify emotional or cognitive changes, analgesia, hypothermia, appetite, mental state, feelings of contentment, and other psychotropic effects. The dosage level and combination with other cannabinoids is critical in helping to combat and reduce anxiety. If used improperly THC can be quite anxiogenic and stimulate or produce anxiety, while lower doses can be anxiolytic and reduce anxiety.  A major factor in treating this disease using THC is dose dependency, finding the appropriate ingestion technique, and how to best combine with other cannabinoids.

      

     The other phytocannabinoid of interest here is CBD (Cannabidiol), and it has been demonstrated that CBD helps play a role in reducing anxiety as a single agent. Once again, the exact role can be dose dependent and work thru several different receptor systems rather than CB1 and CB2 (i.e. VR1 and 5-HT1A). So, whereas THC binds to CB1 and CB2 receptors, CBD has an affinity for the vanilloid receptor VR1, and the serotonin receptor 5-HT1A. These are also some of the dopamine oriented receptors and also involved in serotonin metabolism. Note that many current pharmaceuticals used to treat anxiety/depression also target dopamine and serotonin levels similar to the mechanism of action of cannabis.

 

     CBD also can act as a CB1 receptor antagonist/inverse agonist and thereby limit the effect of THC on the CB1 receptor. This translates into CBD having the ability to reduce anxiety and improve mood by eliminating the anxiolytic effects from too much THC. Noteworthy is that the optimal dose for CBD for its anxiolytic effect is a low or moderate dose, and that higher doses proved no more effective. The entire system of neurotransmitters and receptors is rather complex, and simplified for purposes of this article. But it is obvious that these two cannabinoids are very involved in regulating anxiety or depression thru the above receptors either by activating or inhibiting them.

 

     The studies on the psychological effects of cannabis and THC have unfolded a highly complex scenario. The behavioral and psychological outcomes using cannabis can be highly variable. They range from relaxation, euphoria, heightened perceptions and sociability to panic, paranoia, and possible psychosis. In some studies, chronic use of cannabis has been hypothesized to exacerbate and worsen symptoms of anxiety and depression, and reduce the therapeutic effects from standard anxiolytic pharmacological agents. Other studies show that with the proper dose, strain and technique that anxiety can be reduced using cannabis, and another strain may correspondingly aid in the treatment of depression.

     Because of the limitations in effectiveness of current pharmacology for anxiety disorders, and a host of unwanted/addictive side effects, as well as potential tolerance development, the ability of cannabis to modulate and shape emotional responses in the treatment of anxiety and depression is a welcome mode of treatment. It appears from the consensus of studies that the optimal combination of THC and CBD is critical to avoid a worsening of anxiety, and that too much THC can be anxiolytic, unless it is balanced by the appropriate amount of CBD (a low or moderate dose is best). For depression, it is recognized that a different combination may be needed (i.e. more THC, perhaps a strong sativa, with a low dose of CBD…). There is tremendous variability in both patient’s responses and subjective analysis of outcomes when researching the use of cannabis to treat this disorder.

 

     A drug SATIVEX is patented outside of the US for use for MS, spasticity, and neuropathic pain and has approximately equal ratios of THC and CBD (1.08:1). However, when tested to reduce anxiety, it actually caused slight anxiety and was axiogenic not anxiolytic. This leads to a possible conclusion to use either less THC or more CBD, so in order to best treat anxiety perhaps a ratio of 1:3 is better than equal amounts of these two cannabinoids. A1:3 ratio means one part THC to three parts CBD, or 25% THC and 75% CBD. It can be assumed that terpenes also play a major role in effecting mood, and some have been shown to be anxiolytic or sedating (i.e. limonene, terpinolene, linalool, myrcene). To treat depression, it may require a different strain, dosage, and technique with a higher concentration of THC and stimulating terpenes. Studies on the biological and neurological determinants of different responses to cannabis are still in early stages, partly due to the restrictions of government research, and breakthroughs and new areas of research are advancing rapidly worldwide. These advances may allow for a more unified and personalized approach for the employment of cannabis based medications for use in anxiety and mood disorders.

Anxiety/Depression