Treatment with CBD – Your Gateway to the Science of Cannabidiol
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Treatment with CBD – Your Gateway to the Science of Cannabidiol
We present a comprehensive review about the use of CBD for psychiatric disorders, based on published evidence of over a thousand scientific research studies. We discuss confirmed findings for the following 12 psychiatry therapeutic areas:
It has been long known that the endocannabinoid system plays an important role in acquiring and maintaining drug-seeking behavior through its activation of the reward system and the learning function of the brain. Both the CB and CB2 receptors are important components of the reward circuitry in the central nervous system.
As such, there is evidence that CBD most probably has an effect on craving and the development of withdrawal symptoms. Having said that, the anti-addiction characteristics of CBD are due to its potential to reduce drug memories, both directly and indirectly by disrupting the reconsolidation of drug memories.
The mechanism behind the anti-craving effects of CBD is its agonistic properties on the 5-HT1A receptors. This property is responsible for also regulating the:
Furthermore, CBD also regulates glutamatergic signaling through serotonins and endocannabinoids. The glutamatergic signaling is an important mechanism in both drug seeking and relapse. Having said that, this action of CBD contributes to its potential as a therapeutic agent in treating addictive behaviors.
Watch this 9:11 minute SEIServices animation: “Brain Reward: Understanding How the Brain Responds to Natural Rewards and Drugs of Abuse”
However, it is important to note that CBD might yield a different effect in connection with different substances. For example, in preclinical experiments, CBD was able to reverse cravings and drug seeking behavior related to:
This effect was noted without developing tolerance, sedation, or interference with other behaviors.
Interestingly, CBD by itself did not lead to dependence, while co-administration of CBD and THC did not result in alleviating THC dependence.
Studies assessing the effect of CBD in treating alcohol use disorder, CBD showed potential because it was well tolerated and did not harmfully interact with alcohol.
CBD oil also has potentials in helping people quit cigarette smoking by reducing food and drug cues. In addition, those patients who received CBD compared to those who received placebo exhibited lower levels of pleasantness when they saw smoking-related pictures. As we know, visual cues are an important factor in drug craving.
These studies administered between 100 mg/day and 800 mg/day CBD.
Watch this 4:15 minute Alila Medical Media animation: “Mechanism of Drug Addiction in the Brain”
Health professional have long known about the relationship between cannabis use and psychosis: heavy marijuana smoking is associated with the appearance of psychotic episodes and psychotic-like symptoms.
In addition, heavy cannabis use is also a risk factor for developing schizophrenia, especially when users start at a young age, use frequently and for a prolonged time.
Furthermore, the ratio of THC:CBD is also a factor in developing psychosis: those who use very high THC:CBD products are at much higher risk than those who use cannabis that is rich in CBD. As a matter of fact, people who use THC products that contain no CBD are at the highest risk of psychotic symptoms.
Scientists hypothesize that THC-induced psychosis is due to the overstimulation of the CB1 receptor on glutamatergic neurons. In addition, THC also hyperactivates the endocannabinoid system leading to mental dysregulation and therefore psychosis.
In light of the above, CBD has shown tremendous potential as a well-tolerated and effective treatment option for schizophrenia, with effects similar to standard medications such as clozapine. Doctors expect that CBD is effective not only in combination with antipsychotic medications, but also as a monotherapy (used only by itself).
Watch this 2:33 minute UCTV video: “Symptoms of Psychosis”
The reason behind the anti-psychotic effect is that CBD promotes endocannabinoid signaling, exerts a partially agonist effect on dopamine D2 receptors, and activates TRPV1 pathways.
High levels of anandamide (AEA – a fatty acid neurotransmitter, which is a derivative of an essential omega-6 fatty acid) shows an inverse correlation with psychotic symptoms and frequency of cannabis use. As a matter of fact, high AEA levels are present in patients with schizophrenia, compared to healthy individuals. Scientist hypothesize that high levels of AEA might be an adaptive mechanism to counteract psychosis as opposed to the reason of psychosis. CBD increases AEA levels and thereby indirectly activates CB1 receptors.
Indeed, clinical trials comparing CBD with amisulpride showed similar efficacy, but CBD naturally has much fewer side effects. Moreover, those who took CBD had higher levels of AEA, and higher levels of AEA were associated with a reduction of psychotic symptoms.
Several clinical trials confirmed the effect of CBD against psychosis, and all found that CBD has very high potentials as an antipsychotic medication.
These studies administered between 600 mg/day and 1000 mg/day CBD.
Watch this 8:10 minute Medscape video: “Schizophrenia Overview | Clinical Presentation”
The CB1 receptor plays a major role in learning and responding to emotional events, and also in responding to acute stress, fear, and anxiety response. Studies show that a reduction of CB1 signaling leads to an increase in stress hormones, while an increase leads to increased resilience against stress.
The anxiolytic effect of CBD appeared in several pre-clinical trials. Scientist suspect that this is due to the action of CBD on 5-HT1A receptors. In these experiments, CBD reduced learned fear, fear memory processing, and phobias. The extinction of fear memories occurred via the CB1 receptors.
An interesting aspect is that agents that target endocannabinoids (such as THC and CB1 agonists) have a biphasic effect: low doses decrease anxiety, while high doses increase anxiety. However, CBD does not cause anxiety even when patients take it in high doses. In a study, 300 mg 99.9% pure CBD isolate (but not 150 mg or 600 mg) appeared to be the best therapeutic dose to treat anxiety. Another study used the same dose and found that the effect of CBD for anxiety was similar to the effect of diazepam. A study assessing the effect of CBD on social anxiety disorder found that 600 mg CBD significantly reduced patients’ anxiety symptoms, including fear of public speaking.
Overall, these studies administered between 300 mg/day and 600 mg/day.
Watch this 5:32 minute Osmosis video: “Generalized anxiety disorder (GAD) – causes, symptoms & treatment”
In animal studies, those animals that had deficiency in CB1, showed symptoms of low mood, depression, inefficient coping strategies, and cognitive deficits. In addition, scientists found an inverse relationship between cannabis use and clinical stability of bipolar patients.
However, CBD has shown antidepressant properties, in association with 5HT1A receptor-mediated neurotransmission and CB1 receptor interaction. Moreover, CBD also directly interacts with serotonin pathways by increasing tryptophan levels. So far, however, no completed clinical trials with results exist, only trials in progress.
In these studies, patients received 600 mg CBD per day.
Watch this 3:52 minute Mechanisms in Medicine video: “Understanding Bipolar Disorder”
The anti-inflammatory, anti-apoptotic and neuroprotective characteristics of CBD make it an excellent candidate for clinical trials on the treatment of neurocognitive disorders. Interestingly, though, scientists claim the structure and chemistry of CBD as the source of treatment potential as opposed to its biological function of binding to various receptors.
In mouse models of Alzheimer’s dementia, CBD decreased pro-inflammation mechanisms, and improved face recognition and memory, especially emotional memory. Furthermore, in humans, CBD was more beneficial on cognition than THC or placebo. In these studies, volunteers who took CBD but no THC outperformed those who took placebo or THC on tasks related to memory, psychosocial well-being, switching, verbal learning, and other memory functioning.
In double-blind clinical trials among Parkinson’s and Huntington disease patients, taking CBD oil was associated with better quality of life, with no or fewer side effects than traditional medications. On the other hand, when given THC/CBD combination medications, these patients did not significantly improve.
Patients in these studies took 200-300 mg CBD per day.
Watch this 2:42 minute Health Apta video: “Causes of neurocognitive disorders”
Endocannabinoids play a role in sleep disorders as well: decreased endocannabinoid activity is linked to poor sleep and increased waking, while its activation leads to enhanced sleep.
There is, however, a dual effect in this domain as well: low CBD doses are associated with shorter time to fall asleep, while high doses lead to longer sleep onset times. Scientists suspect that CBD acts on circadian clock genes and the production of melatonin. CBD also increases wakefulness when a person or animals is exposed to light.
Some clinical trials and a large number of case studies attest to the potential of CBD in treating sleep disorders, especially insomnia and parasomnia (meaning: unwanted behaviors and dreams while asleep), and PTSD-related sleeplessness. At the same time, patients did not experience such improvement if they took THC alone or in combination with CBD.
However, there are different results considering the effect, and sustainability of the effect. The reason might be that different studies used different dosages, and some used CBD concurrently with THC.
Patients in these studies took 300 mg CBD per day.
Watch this 3:45 minute video by Dr. Elliott Lee: “Sleep Disorders”
The use of CBD in treating personality disorders is not well stablished, but certain personality traits, such as sensation and novelty seeking, are associated with recreational use of cannabis. In a clinical trial, participants who inhaled CBD compared to those who inhaled THC or a combination of THC and CBD, showed better facial emotion recognition, and CBD mitigated the negative effects of THC.
In these studies, participants took 16 mg CBD daily either alone or in combination with 8 mg of THC.
Watch this 1:45 minute video by Choose Psychiatry: “Personality Disorder”
Marinol (dronabinol) is an approved THC medication to treat nausea and vomiting in cancer patients receiving chemotherapy, and to induce appetite in AIDS patients. Nabilone, a synthetic THC medication, is also an approved mediation to treat nausea and vomiting due to cancer chemotherapy. While Rimonabant, a CB1 receptor antagonist, received approval, it was withdrawn in 2008 because too many people suffered serious psychiatric side effects.
So far, very little information exists on how other cannabinoids affect eating disorders other than cancer and AIDS related eating co-morbidities. We suspect that both THC and other cannabinoids may act on appetite and weight, but we are not exactly sure how, and how this could be used to treat eating disorders. So far, no clinical trials examined this question, but there is indication that CBD might be a promising candidate.
Watch this 2:39 minute video by SickKidsInteractive on eating disorders
Given the serotonergic effect of CBD, which is also involved in OCD, CBD is a candidate in treating OCD. In pre-clinical models, CBD showed promising results in reducing compulsive behavior. So far, however, no human clinical trials exist despite these promising pre-clinical trials.
Post-traumatic stress disorder (PTSD) is a developed response to traumatic events. As such, it is related to anxiety disorder. Inhibition of the endocannabinoid system can result in heightened and chronic stress activity of the body. Therefore, CBD is a promising candidate for treating PTSD symptoms by inhibiting either the reuptake or the degradation of endocannabinoids.
There is preliminary evidence that medical marijuana might improve many of the PTSD symptoms, including anxiety and sleep difficulty, and help extinguish traumatizing memories. Indeed, the 5HT1A antagonistic function of CBD takes place in those brain areas that are linked to defensive responses.
Having said this, other research shows that CBD reduced learned fear levels, the expression of fear, disrupted the reconsolidation of memories, and enhanced psychological extinction. These functions are all relevant to PTSD, and indeed they were confirmed in a double-blind placebo controlled clinical trial. In another clinical trial, CBD decreased PTSD symptom severity in almost all participants, while nabilone decreased the occurrence of nightmares and daytime flashbacks.
In addition to the above studies, there are a number of ongoing clinical trials testing the effectiveness of CBD in treating PTSD. These studies involve the use of CBD oil, high CBD content marijuana, and a combination of CBD and psychotherapy.
Patients in these studies take 400 mg CBD per day (orally). In one study, they inhaled 32 mgs of CBD.
Watch this 2:02 minute video by Beating Anxiety: “PTSD Symptoms And Signs (Post Traumatic Stress Disorder)”
Only published medical case reports and no clinical trials exist to support the effectiveness of CBD in treating dissociative disorders. One trial explored the effect of ketamine with and without CBD and found some small improvements in depersonalization and derealization symptoms.
Patients in these studies received 600 mg CBD daily.
Sufferers of somatic disorders, such as chronic pain, glaucoma, nausea/vomiting, and Tourette syndrome may also benefit from taking CBD. The reason for this hope is the neuroprotective, antiepileptic, anti-asthmatic, and anti-inflammatory properties of CBD. As we saw in our other post on the potential of CBD in the treatment of pain, CBD is a strong candidate as a pain medication.
In addition, both pre-clinical and human studies showed promising potential of CBD in the treatment of irritable bowel syndrome. Scientists believe that this therapeutic effect is due to the action of CBD on the CB1 receptor in the mucosal membrane and neuromuscular layers of the colon and its potential to inhibit and regulate gut movement.
Bonaccorso S, Ricciardi A, Zangani C, Chiappini S, Schifano F. Cannabidiol (CBD) use in psychiatric disorders: A systematic review. Neurotoxicology. 2019 Sep;74:282-298. doi: 10.1016/j.neuro.2019.08.002.