Autism

The core diagnostic features of Autism Spectrum Disorder (ASD) (American Psychiatric Association) include:

1. Persistent deficits in social communication and social interactions, including difficulty communicating thoughts and feelings, deficits in social-emotional reciprocity, non-verbal communication, and adjusting behaviors to suit variable social contexts;
2. Restricted, repetitive interests or behaviors; and
3. Onset during childhood

ASD may be accompanied by comorbid symptoms and conditions, including:

1. Agitation (self-injury, disruptive behaviors)
2. Disrupted sleep
3. Feeding issues
4. Co-occurring psychiatric symptoms/diagnoses (anxiety, specific phobia, obsessive compulsive disorder, ADHD, major depressive disorder, oppositional defiant disorder, psychotic disorders)
5. Epilepsy

As of March 2021, there is no evidence from clinical trials to support the conclusion that medical cannabis or cannabinoids are useful or effective in the treatment of the core symptoms of ASD.

There are limited observational reports (Aran et al., 2018; Schleider et al., 2019; Barchal et al., 2019) and 1 placebo-controlled trial (Aran et al. 2021) showing possible short-term benefits of an orally-administered cannabidiol-predominant cannabis extract preparation with a CBD:THC ratio of 20:1, in the treatment of comorbid problems with agitation and other severe behaviors in children and young adults with ASD that have been refractory to standard treatments.

There is no clinical data regarding the long-term safety or efficacy of cannabis or cannabinoids in the treatment of comorbid symptoms of agitation or other severe behavioral problems in individuals with ASD. 

Based on very limited short-term clinical data outlined above, and no clinical studies looking at long-term efficacy or safety, the Department of Health and Human Services (DHHS) in collaboration with a group of recommending medical providers and researchers concludes that currently there is insufficient evidence to support or refute the conclusion that medical cannabis or cannabinoids are effective or ineffective in the treatment for comorbid symptoms of agitation in individuals with ASD.

Comorbid agitation and other severe behavioral problems in individuals with ASD can be challenging to manage and may not adequately respond to non-pharmacologic and FDA-approved pharmacologic interventions. Because of the severity of symptoms, lack of adequate response, and side effects from other treatments, some individuals and/or their caretakers may consider using cannabis-based products for the management and control of agitation and complex behavioral problems associated with ASD that are not adequately managed with usual treatments (Aran et al., 2018).

If the decision is made to attempt to manage agitation and other complex behavioral problems in an individual with ASD using cannabis/cannabinoid preparations, the healthcare provider, the individual (if possible), and their caretakers should understand the following prior to proceeding:

1. There are no clinical trials evaluating the long-term effectiveness and safety of using any cannabis-based medicines in the treatment of agitation associated with ASD;
2. Use of cannabinoid products containing THC during critical periods of child and adolescent brain development may result in short-term and/or long term adverse effects on neurocognitive functions, including learning, memory, and attention (Dharmapuri et al., 2020; Schonhofen et al., 2018);
3. Use of cannabis-based medicines containing THC may result in the development of psychosis, which may or may not be reversible (Dharmapuri et al., 2020; Schonhofen et al., 2018);
4. Individuals with ASD may be more likely to develop cannabis-related psychosis than those who do not have ASD;
5. The onset of psychosis due to THC may not be immediate and may not show up for months to years after starting treatment with THC-containing cannabis preparations;
6. Detection of symptoms of psychosis due to the use of THC-containing cannabis preparations in individuals with ASD may be delayed and more difficult to detect due to the core problems with communication that characterize individuals with ASD; 
7. There may be undiagnosed underlying conditions feeding comorbid symptoms of agitation in individuals with ASD that may respond to appropriate non-cannabinoid interventions, sparing the costs and risks of the unnecessary use of cannabis/cannabinoids; and
8. The single placebo-controlled study that showed possible benefit of using a cannabis extract in management of comorbid agitation associated with ASD used a CBD-predominant oral preparation containing a CBD:THC ratio of 20:1 (Aran et al., 2021).

Based on observational data and the single placebo-controlled trial referenced above, the following may be considered as a possible starting point for use of medical cannabis for treatment of comorbid agitation in individuals with ASD:

• Suggested chemotype: Chemotype III, CBD predominant (20:1) CBD:THC ratio
• Dosage form: Cannabis extract prepared for oral or sublingual use
• Route: Sublingual drops
• Starting dose and titration: Dose range for efficacy is likely quite variable depending on unknown or unpredictable individual patient factors. In the placebo-controlled trial, the following dose titration regimen was used (Aran et al., 2021):
  • Starting dose: 1 mg/kg/d CBD (and 0.05 mg/kg/d THC).
  • Titration: increase dose by 1 mg/kg/d CBD (and 0.05 mg/kg/d THC) every other day up to 10 mg/kg body weight per day CBD (and 0.5 mg/kg/d THC) for children weighing 20–40 kg or 7.5 mg/kg/d CBD (and 0.375 mg/kg/d THC) for weight > 40 kg.
  • Maximum dose: 420 mg CBD and 21 mg THC per day, divided into 3 daily doses.
• Slower, more gradual up-titration than every 2 days, with careful monitoring for adverse reactions and desired clinical outcomes, may be more appropriate in real-world nonclinical-trial settings.
• Careful monitoring for difficult-to-detect adverse reactions from use of cannabis-based products, including psychosis, should be done by a provider with clinical expertise assessment and management of patients with ASD and comorbid conditions.