CBD has gained incredible popularity in recent years as a kind of home remedy for just about anything. With the passage of the 2018 Farm Bill here in the U.S. and the full legalization of industrial hemp cultivation, this popularity is sure to grow even faster. But what does the research have to say? Here we cover some of the most recent findings regarding CBD’s efficacy as a treatment for a number of conditions.
CBD Clinical Trials
The press on medical marijuana use is fraught with misunderstandings and misconceptions. At times, the politics around legalization has caused problems in studying its medical uses. Cannabis use through smoking or non-medical preparations can have many risks, especially in the developing brains of adolescents. Cannabis is a complex substance containing up to 750 chemicals, including 104 cannabinoid compounds, of which the majority have unknown effects, interactions and side effects.
Studying the components in medical settings and for treatment of certain conditions requires purification and isolation of specific compounds. Uniformity of dosage and administration are critical in order to confidently investigate the potential benefits and side effects of medicinal use. This article seeks to summarize the latest scientific findings on CBD and to clarify some misconceptions.
What is CBD?
CBD stands for Cannabidiol. It is one of the many chemical entities produced by the cannabis sativa plant and is also known in the scientific community as a “cannabinoid” in terms of its chemical composition. It is important to make a distinction between CBD and the well-known cannabis sativa plant, which most people think of as marijuana. In truth, the whole plant contains many other compounds, such as THC (Delta9-Tetrahydrocannabinol), which is the primary psychoactive component. By contrast, CBD is non-psychoactive.
Neurochemistry and CBD
CBD works on a cannabinoid signaling system in the brain, which is found in both invertebrates and advanced vertebrates called the endocannabinoid system. This signaling system plays a role in regulating pleasure, memory, thinking, concentration, body movement, awareness of time, appetite, pain, and sensory processing as well as brain development. CBD appears to have a neuroprotective and anti-inflammatory effect on the brain, leading researchers to look at many applications in medicine for a number of disorders.
CBD Oil Effects
CBD Oil has been shown to have many potential benefits, including anxiety relief, anti-seizure effects for epilepsy, neuroprotective effects for the brain, pain relief, and cancer treatment.
Does CBD Get You High?
Cannabidiol does not cause the high associated with the more well-known compound THC. CBD is non-psychoactive and thus may deliver considerable benefits without the adverse effects associated with marijuana as it is commonly used.
Is CBD Addictive?
CBD is not addictive. In fact, it has been studied as an intervention for addictive behaviors, given that it might have may have therapeutic properties on opioid, cocaine, and psychostimulant addiction.
Is CBD Safe?
A review of the scientific data shows that generally, cannabidiol is considered safe for some clinical indications. It has comparatively fewer side effects than most prescription medications. The majority of the research has occurred in patients with treatment-resistant epilepsy and psychotic disorders. Much more research is needed in human trials to determine its safety for other disease states and indications. Also, animal research shows that effectiveness is highly dose-dependent so it is important to pay close attention to the instructions for use.
CBD Side Effects
The most commonly reported side effects of cannabinoids are tiredness, diarrhea and changes in appetite or weight. Additional clinical trials and safety profiles are needed for many conditions that have not yet been adequately studied in humans.
CBD Clinical Trials: What The Research Says
Research on chemical compounds always begins in the lab, typically in vitro before it even gets to animal models or to humans. The biochemical mechanisms of the compound must be well determined in order to more safely perform research with living organisms. A relevant review of cannabinoid safety and side effects both in clinical and animal studies from 2017 can be found at this link. The following is a summary of the research on several neurological conditions in which CBD has been investigated.
One of the most highly studied uses for CBD is in seizure treatment for epilepsy patients. In 2015 the first large-scale multi-center study was presented on 214 patients with Dravet syndrome, Lennox-Gastaut syndrome and several other intractable pediatric epilepsies. Results showed a median reduction in seizures of 36.5%. Limitations of this study included a lack of control group, an open-label observational nature and a short follow up of only 12 weeks.
In 2016 an Israeli study of 74 patients were treated with an oil containing a 20:1 ratio of CBD to THC. The reduction in seizure frequency was 89% and included improvements in behavior and alertness, language, communication, motor skills, and sleep. Study limitations included a lack of control group, reliance on parental report for seizure activity a short duration of the study and lack of measurement of other drug levels. In May 2017, a double-blind, placebo-controlled trial by Devinsky et al was published in the New England Journal of Medicine. The percentage of patients who had at least a 50% reduction in convulsive seizure frequency was 43% with CBD compared with 27% with the placebo group.
In March 2018, a randomized, double-blind, placebo-controlled trial was conducted at 24 clinical sites with 171 participants in the United States, the Netherlands, and Poland. This study reported a reduction in monthly drop seizures of 43.9% in the CBD group versus 21.8% in the placebo group. Reported side effects were minor and similar to previously described studies. An ongoing open-label extension of this trial aims to understand the dose-response effect as well as the long-term efficacy of this therapy. The medication being used for this trial is Epidiolex, a solution containing CBD that was approved for medical use by the FDA in June 2018. This approval was specifically for the treatment of Lennox-Gastaut syndrome and Dravet syndrome, which are both severe forms of epilepsy that are often resistant to normal epilepsy medicine.
The preclinical evidence strongly supports CBD as a potential treatment for generalized anxiety disorder, panic disorder, social anxiety disorder, obsessive-compulsive disorder, and post-traumatic stress disorder (PTSD). This has been limited to acute administration rather than long-term use. Few human studies have yet investigated chronic CBD dosing and more research is needed in this area. A study using rats indicated that cannabidiol could disrupt the consolidation of specific and generalized fear memories. This study may help researchers understand the mechanism behind the effects in the endocannabinoid system, and may hold promise for sufferers of PTSD and other anxiety-related disorders.
There is early evidence that cannabinoids have potential for treating autism or autism spectrum disorder (ASD), a neurodevelopmental disorder that develops in infancy or childhood. The main symptom of ASD is impaired social interaction. Early signs can include unresponsiveness to people, avoiding eye contact or failure to respond to their own names. Researchers have found a potential link between autism and the cannabinoid 2 (CB2) receptors in the brain. Pennsylvania and Minnesota are the only states as of July 2018 to have approved medical cannabis treatments for autism. Research and evidence are still limited on this condition, with no large-scale clinical study results available and only single case study reports and animal research published to date.
Psychosis and Schizophrenia
Schizophrenia is characterized by deficits in learning, memory, attention and executive functioning, and it can severely impact daily living. Antipsychotic drugs have limited benefits and thus novel treatments are being investigated. CBD has anti-inflammatory and antipsychotic-like properties, so may hold promise for schizophrenia. However, a review of the literature in 2017 found that, though CBD has been found effective in improving cognition in pre-clinical or animal models, only one human trial has been conducted with negative results. This indicates a need for further research prior to implementing treatments at this time.
Cannabidiol is thought to modulate various neuronal circuits involved in drug addiction. Much of the work in this area has been done on pre-clinical or animal models, with limited human studies to evaluate. In animal studies, CBD was found to have an impact on the intoxication and relapse phase of opioid addiction. Data on its effect during the withdrawal phase remain conflicting and vary based on co-administration of other cannabinoids such as THC.
A study of 24 smokers who wished to stop smoking and used an inhaler showed that 1 week and 2 weeks following treatment there was a reduction in cigarettes smoked as well as cravings. However, this was a short-term study with a limited population. Other single case studies have been documented on cannabis-related addictive behaviors but further research is needed to generalize the findings. The NIH recently authorized a 3.8 million dollar 5-year study to be conducted at Albert Einstein and Montefiore Health System to examine whether medical marijuana reduces opioid use among adults with chronic pain, including those with HIV.
Parkinson’s disease is a motor neurodegenerative disorder. The main feature is a progressive death of nigrostriatal dopaminergic neurons, resulting in bradykinesia, rigidity, and tremor as major motor abnormalities. There is no known cure, and the most potent treatment to date, levodopa, commonly results in long-term motor complications after chronic use. These include wearing off and dyskinesia, or difficulty in performing voluntary movements. A review in the journal Pharmacology and Therapeutics shows that a neuroprotective effect exerted by CBD has been found in animal models. A few trials have been conducted with small numbers of participants, using CBD in addition to their usual levodopa therapy. One trial of 21 patients showed significant improvements in measures of well-being by Parkinson’s patients. However, no statistically significant difference concerning motor symptoms was reported.
The Final Word on CBD Clinical Trials
Interest and research in CBD as a potential treatment for many brain-related indications is accelerating due to some promising results in early trials. This article explores some of the clinical and pre-clinical research that has been conducted to investigate its possible role in treatment. Other possible applications include Alzheimer’s disease, chronic pain, multiple sclerosis, cancer, Huntington’s disease, and other inflammatory conditions. While it is too early for some therapies to be applied in a clinical setting, new discoveries will continue as researchers begin to understand the mechanisms of the endocannabinoid system and CB2 receptors. As more clinical study evidence becomes available, patients may have new and better alternatives to treatment.