I have long been interested in the possible use of cannabis plant extracts as a way of treating seizures, anxiety, and some of the maladaptive behaviors observed in autism spectrum disorders.  Indeed, my family has played a prominent role in advocacy efforts to legalize the use of cannabinoids; and, as a consequence, my grandson became the first patient to use these compounds in the state of Utah.  Unfortunately, cannabinoids didn’t control my grandson’s seizures.  His convulsions only remitted after strict adherence to a ketogenic diet.  However, many other friends and patients within our clinics have experienced better results.  For many reasons, I look forwards to the day I am able to conduct a clinical trial using cannabinoids in conjunction with transcranial magnetic stimulation (TMS).  I do believe that their concurrent use would provide for synergistic effects.

The term cannabis encompasses a group of flowering plants having two main species: hemp and marijuana.  These plants have thousands of chemical compounds that can be derived and concentrated by an extraction process involving multiple steps (e.g., distillation, expression or “cold pressed”).  (Note: In the essential oils industry, the extraction process is used in order to obtain aromatic compounds that promote healing of skin injuries, relaxation and/or sleep [e.g., lavender, tea tree, eucalyptus oil]).  The end result of the extraction process is a crude mix of many chemicals that may include undesirable elements.  The crude mixture is then refined to remove the undesirable chemicals thus providing an important step for quality assurance.  It is unfortunate that much of the safety conferred by the refining process is negated by an industry that is presently allowed to self-police itself.  This has fostered a chemical industry that lacks in health and safety standards.  As an example, commercial verbiage such as a cream containing “CBD-rich” products may serve to hide the widely fluctuating percentages of CBD oil that may exist in a given formulation. In this scenario, the buyer assumes all of the risks even in the face of misleading advertisement.  Let the buyer beware!

Refined cannabis products are sold in many different forms intended for topical, smokable, or ingestible use.  Regardless of the medium of administration, these chemicals ultimately act on receptors within the nervous system.  These receptors comprise part of a regulatory system, the “endocannabinoid system”,  that mediate a wide-ranging set of physiological functions, e.g., fertility, pregnancy, appetite, pain-sensation, mood.  I have been specially attracted to research that indicates how medical cannabis increases inhibitory neurotransmission and rescues autistic-like social behaviors in mouse models of the condition (Kaplan et al., 2017).  As previously stated, I believe that using these compounds along with TMS may provide for synergism in alleviating the inhibitory deficit observed in ASD.

The two best known compounds derived from the extraction of the cannabis plant are tetrahydrocannabinol (THC) (a psychoactive compound producing a sense of euphoria) and cannabidiol (CBD) (a non-psychoactive compound with some therapeutic value in the treatment of aches and pains [arthritis], anxiety and panic attacks).  Some people have said that CBD is the yang to THC’s yin; it ameliorates anxiety without producing a “high”.  CBD is also known as “hemp oil” due to the fact that it is usually extracted from this plant species.  Hemp has little, if any, THC. It is legal, in all 50 states, to sell CBD with less than 0.3% THC.  Formulations with higher levels of THC may be obtained if prescribed by a license physician.  To check those states in the US where the use of cannabinoids has been legalized visit:  see http://www.ncsl.org/research/health/state-medical-marijuana-laws.aspx?fbclid=IwAR2GYvhwhcVJe1ZYKvV3n6r87nJ6buTQZ0rCPdi61N9CKqgFYa-vaDzfePM 

Although the modern press conveys the use of CBD as a trendy cure all, the amount of information derived from clinical trials has been surprisingly limited. Interest has been spurred by the FDA’s approval of a pharmaceutical grade CBD elixir (Epidolex) for treatment of two rare types of childhood epilepsy: Lennox-Gastaut syndrome and Dravet syndrome.  According to research published in 2017 by the Journal of Epilepsy Research: “The results of these studies demonstrate that, at a dosage of 20 mg/kg/day, CBD added on to pre-existing AED treatment is superior to placebo in reducing the frequency of convulsive (tonic-clonic, tonic, clonic, and atonic) seizures in patients with Dravet syndrome, and the frequency of drop seizures in patients with Lennox-Gastaut syndrome. In the latter patients, a dosage of 10 mg/kg/day treatment was also superior to placebo. Therefore, there is now for the first-time, class 1 evidence that CBD improves seizure control when added on to other AEDs in patients with two difficult-to-treat epileptic encephalopathies.”

The Institute of Medicine has also issued its conclusions about the potential therapeutic effects of marijuana extracts: “Scientific data indicate the potential therapeutic value of cannabinoid drugs, primarily THC, for pain relief, control of nausea and vomiting, and appetite stimulation; smoked marijuana, however, is a crude THC delivery system that also delivers harmful substances. The psychological effects of cannabinoids, such as anxiety reduction, sedation, and euphoria can influence their potential therapeutic value. Those effects are potentially undesirable for certain patients and situations and beneficial for others. In addition, psychological effects can complicate the interpretation of other aspects of the drug’s effect.” https://www.nap.edu/catalog/6376/marijuana-and-medicine-assessing-the-science-base

The interest for using CBD in ASD has been prompted by a preliminary study published in the Scientific Reports of the journal Nature ( Schleider et al., 2019).  According to the abstract: “…the data [was] prospectively collected as part of the treatment program of 188 ASD patients treated with medical cannabis between 2015 and 2017. The treatment in majority of the patients was based on cannabis oil containing 30% CBD and 1.5% THC. Symptoms inventory, patient global assessment and side effects at 6 months were primary outcomes of interest and were assessed by structured questionnaires. After six months of treatment 82.4% of patients (155) were in active treatment and 60.0% (93) have been assessed; 28 patients (30.1%) reported a significant improvement, 50 (53.7%) moderate, 6 (6.4%) slight and 8 (8.6%) had no change in their condition. Twenty-three patients (25.2%) experienced at least one side effect; the most common was restlessness (6.6%). Cannabis in ASD patients appears to be well tolerated, safe and effective option to relieve symptoms associated with ASD.” In another study on 60 children on the spectrum 80% of children who had not shown improvements with conventional therapies showed decreased disruptive behavior and anxiety, half showed improvement in communication and 40% showed significant improvements in anxiety.  Adverse effects included sleep disturbances (14%), irritability (9%) and loss of appetite (9%) (Aran et al., 2019). In other studies  it has been suggested that CBD therapy potentially targets core pathological features of ASD.  Indeed, animal models of ASD have shown a dysregulation of the endocannabinoid system and CBD may serve to normalize the same.

My personal (anecdotal) experience suggests the utility of CBD for stimming, agitation, and some self-injurious behaviors.  Indeed, patients seemingly become less restless, collaborate better with parents and teachers, and are able to better sit and pay attention at class.  Changes, if they occur, are noted fairly fast, in the first few weeks of treatment.  I have found CBD to be a useful preventive strategy in autistic individuals who are receiving neuroleptic medication thus lowering their seizure threshold.  Side effects of cannabinoids include somnolence, decreased appetite, diarrhea, inhibition of hepatic drug mechanism, dry mouth, lightheadedness, euphoria, and low blood pressure.  Additional concerns to be kept in mind include the lack of industry regulation regarding their manufacturing/sales, large variability in purity between products, and the amount of THC content.  Also, like any other crop, plants are prone to pests and disease.  Ultimately, the use of pesticides in cannabis plants may lead to higher levels of these chemicals than those legally allowed for edible or smokable products.

References

Aran A, Cassuto H, Lubotzky A, Wattad N, Hazan E. Brief report: cannabidiol-rich cannabis in children with autism spectrum disorder and severe behavioral problems0 a retrospective feasibility study. J Autism Dev Disord doi: 10.1007/s10803-018-3808-2 [Epub ahead of time]

Kaplan JS, Stella N, Catterall W, Westenbroek RE. Cannaidiol attenuates seizures and social deficits in a mouse model of Dravet syndrome. PNAS 114(42):11229-11234, 2017.

Schleider Bar-Lev, et al. Real life experience of medical cannabis treatment in autism: analysis of safety and efficacy. Scientific Reports 9: article 200, 2019.

Those interested can read our previous blog on alternative therapies: Do you believe in magic?