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An Overview of Autism Spectrum Disorder Pharmacological and Therapeutic Drugs

Currently, in the United States, autism spectrum disorder has no cure or known drugs to treat it. However, some medications can help certain social and behavioral symptoms associated with autism. The U.S. Food and Drug Administration (FDA) has so far approved only two antipsychotic drugs for autism irritability treatment: risperidone and aripiprazole (LeClerc and Easley, 2015). However, both have a serious side effect of weight gain leading to high levels of obesity in individuals with autism; children with autism are about two times more likely to be obese than children without developmental disabilities, and a third of children with autism are severely overweight (Phillips et al., 2014). Children who are overweight are more likely to be teased or bullied, causing social isolation (Craig et al., 2004; as cited in Hill et al., 2015), and for children with autism, the social implications can further increase the difficulty autistic individuals have with social communication and interaction. Additionally, the risk for lifelong health conditions related to obesity such as asthma and diabetes increases. While several factors contribute to obesity in autistic children, weight gain from certain medications only further exacerbates the risk of obesity.


Other drugs used for treatment, like antidepressants, are controversial because of the risks and side effects. Sertraline, a selective serotonin inhibitor (SSRI), is a common antidepressant prescribed to treat anxiety, self-injury, and aggression in autistic individuals (Potter et al., 2019). However, adverse side effects include diarrhea, insomnia, increased energy, impulsivity, and decreased concentration (Hollander et al., 2012). The treatment plan of patients with autism usually has a conglomerate of medications in addition to their behavior and communication therapies. With insufficient medications to treat the symptoms of autism, the process of finding a medical regimen that work with very few side effects can be frustrating. Oftentimes, distressed caregivers will research other alternatives if the current regimen is not working for the patient, like complementary health approaches (CHAs), which comprises alternatives developed outside of mainstream medicine and practices. Examples of CHAs are natural products like vitamins and herbal supplements (Duvall et al., 2019). In recent years, researchers have been researching potential alternatives that may seem unconventional for today’s standards, including cannabidiol found in marijuana, 3,4-methylenedioxymethamphetamine (MDMA), and Chinese herbal medicine. Cannabidiol has been found to have the potential in treating severe behavioral problems in autistic children (Aran et al., 2019). MDMA, which is already in the process of becoming a treatment for post-traumatic stress disorder, has been found to have potential in treating social anxiety in autistic adults (Danforth et al., 2018). Chinese herbal medicine, although with less research, has been found to improve inattention, seizures, and behavioral outbreaks (Cai et al., 2015). This paper aims to explore the aforementioned alternative medications for autism treatment, and additionally, the importance of keeping an open-minded outlook when treating the symptoms of an intricate condition to increase the quality of life of autistic individuals.

There are two main cannabinoids in the cannabis plant: tetrahydrocannabinol (THC) and cannabidiol (CBD). THC is the psychoactive component often associated with the negative consequences of cannabis use. The recreational use of cannabis can cause negative effects like decreased motivation, cognitive decline, and even schizophrenia (Aran et al., 2019). CBD, instead, has been shown to have potential anxiolytic and anti-inflammatory effects that can help treat anxiety, chronic pain, and insomnia (Campos et al., 2017 as cited in Aran et al., 2019). With cannabis as a treatment alternative increasing in popularity due to the medical benefits and legalization of medical usage, growing interest in CBD treatment in the autism community is also increasing. In recent years, cannabis has increasingly been considered a CHA. Since many children with autism suffer from disruptive behavior such as tantrums, self-injury, and violence, the difficulties can increase social isolation and cause distress to caregivers (Maskey et al., 2013; as cited in Aran et al., 2019). Consequently, distressed parents often seek to find alternative treatments such as CBD when standard behavioral and medical treatment do not work.


A study on CBD-rich medical cannabis in children with autism done by Aran et al., “Brief Report: Cannabidiol-Rich Cannabis in Children with Autism Spectrum Disorder and Severe Behavioral Problems—A Retrospective Feasibility Study”, have found that CBD could be an alternative in improving severe disruptive behavior in children with autism. The study was done on a sample of 60 children with an average age of 12 years old, who were prescribed a cannabis oil solution to be given 2-3 times daily for four weeks. All children were diagnosed with autism and severe behavioral problems. The results have shown that CBD treatment is promising; there was considerable improvement in behavior problems reported in 61% of the children, in anxiety in 39% of the children, and communication of problems reported in 47% of the children. However, the results have also shown that there were some adverse events reported by parents throughout the treatment. Common adverse side effects were restlessness, irritability, and loss of appetite but could be resolved by adjusting or omitting doses. After treatment, behavioral outbreaks “were much improved” or “very much improved” in 61% of the children, with 33% receiving either fewer medications or lowered dosages, and 24% stopped taking medications altogether. Only 8% of the children received more medications or increased dosages. While the study is not conclusive due to the small sample size, it does show that CBD treatment can potentially treat harmful, disruptive behavior in autistic children; it may even also help decrease the number of medications taken which save both money and chance of adverse side-effects.


In the case of a non-laboratory setting, Duvall et al.’s report of a four-year-old autistic child with self-injurious behaviors treated with CBD shows the potential benefits of CBD may outweigh the unknown and possible risks when all other therapies are exhausted. The case study examined the young boy’s circumstances and the rationale behind his parents’ decision to use CBD treatment. After intensive applied behavioral analysis (ABA) therapy and prescribed medications, the family saw no significant improvement in their son’s behavior and was reluctant to try other medications because they were concerned about the potential side effects. Risperidone had caused side effects like decreased responsiveness, and the seizure medication Valproate was attempted but discontinued due to severe diarrhea. When their friend – a fellow parent of a son who also has autism – recommended an “herbal supplement”, the parents of the case study’s subject decided to take a chance. The nonverbal four-year-old boy had hypotonic cerebral palsy and visual impairment, making his case of autism complex and difficult to treat. Most importantly, his propensity for self-harm included headbanging, and consequently, was issued a protective helmet and arm splints to prevent bruises and further injury. After giving their son a drop of the CBD solution once a day, the parents observed a calmer and more relaxed change in his behavior. Notably, for the first time in months, the mother was even able to remove her son’s helmet and wash his hair. However, the parents reported that once they discontinued the CBD treatment when they realized the solution was made from distilled cannabis leaves, the self-harm behaviors of their son quickly resurged. In the conclusion of Duvall et al.’s case study, a consulted doctor recommended a benzodiazepine to the parents because of the uncertainties and lack of information about CBD regarding children with autism.

While Duvall et al.’s case study cannot generalize what CBD can do for all children with autism, there are several issues to examine from the one case family’s circumstances. First, in severe cases of autism, evidence-based therapies have a less likely outcome of positive results (Itzchak & Zachor, 2014, 2011; as cited in Duvall et al., 2019). The long process of trying medication after medication to mitigate the symptoms of autism can be long and arduous. The side effects of these medications can even worsen the child’s condition, as seen in Duvall et al.’s case when Risperidone had caused decreased responsiveness in the four-year-old subject. Second, while some families are able to get treatment for their children, conventional behavioral treatments of autism are harder to access for other families (Vohra & Sambamoorthi, 2014, Kogan et al., 2008; as cited in Duvall et al. 2019). Factors like high costs, lack of knowledge, scarcity of providers, and insurance coverage are the main contributors. CBD may not be the cure for all of autism’s symptoms, but it may be an alternative with fewer side effects and easier access. Although there is no conclusive answer yet, the promising findings and results from various studies show that it is worthwhile to further explore cannabidiol-rich cannabis as a treatment for children with autism. For now, the Drug Enforcement Administration (DEA) has classified cannabis in the Schedule I category, which labels the drug as having no currently accepted medical use and possible high potential for abuse. With cannabis in the most strictly regulated category, this makes funding for research harder to obtain and prescribing almost impossible. There is still much to be known about cannabis and the future of CBD treatment so moving cannabis to a Schedule II substance is highly recommended to facilitate further research studies on CBD treatment for autism and other medical conditions.

The psychoactive compound 3,4-methylenedioxymethamphetamine (MDMA) is most commonly found in the popular rave drugs known as Ecstasy or Molly, which frequently contain unknown and sometimes dangerous substances. However, under laboratory settings, pure MDMA has been proven to be safe for consumption when taken in limited and moderate doses (Danforth et al., 2016). The Multidisciplinary Association for Psychedelic Studies (MAPS) is a non-profit research organization that is primarily focused on studying MDMA-assisted psychotherapy. MAPS has helped the therapy be recognized for its treatment of posttraumatic stress disorder (PTSD), an anxiety-related disorder, and is currently in the midst of Phase 3 trials, meaning FDA approval will allow for its prescription for PTSD treatment (Danforth et al., 2016). When used with psychotherapy, MDMA allows individuals to “confront and consider emotionally intense memories, thoughts or feelings” and can increase “empathy and compassion for others and one’s self” (Bouso et al, 2008, Greer and Tolbert, 1986, Mithoefer et al., 2011; as cited in Danforth et al., 2016). Therefore, individuals that take MDMA may see improvements in self-esteem, ability to communicate with others, trust, and intimacy (Grinspoon and Bakalar, 1986; as cited in Danforth et al., 2016).


While MAPS mainly researches MDMA’s benefits for PTSD, the organization also has an MDMA-assisted psychotherapy pilot study for autistic adults with social anxiety. Social anxiety is defined as the “fear of scrutiny and avoidance of social interactions” (American Psychiatric Association, 2013; as cited in Danforth et al., 2016). This fear and avoidance can cause distress or impairment in school, work, and relationships, which can lead to a low quality of life (Liebowitz et al., 1985, Turner et al., 1986; as cited in Danforth et al., 2016). MDMA has been found to have the potential to treat social anxiety in adults with autism because it helps promotes feelings of social affiliation and reduce social fear and avoidance that many autistic individuals face. Unlike most medications that are taken chronically, MDMA-assisted therapy is meant to be administered only a few times with lasting effects. A holistic combination of MDMA and psychotherapy, supportive preparation, and integrative aftercare is needed for results to be effective and long-term.


In a study done by Danforth et al, “Reduction in Social Anxiety after MDMA-Assisted Psychotherapy with Autistic Adults: a Randomized, Double-Blind, Placebo-Controlled Pilot Study”, autistic adults following MDMA-assisted psychotherapy have shown improvement in social anxiety symptoms. The study was done on a sample of twelve autistic adults with severe social anxiety, who were then either randomly given MDMA or a placebo during two psychotherapy sessions. Eight participants received MDMA at various doses while four participants received the placebo. The psychotherapy sessions were 60-90 minutes and occurred over six months. The self-rating Leibowitz Social Anxiety Scale (LSAS) questionnaire was used to measure anxiety levels from baseline to one month after the second experimental session then measured again six months after the final experimental session. The study’s results showed that LSAS score improvement was significantly greater for the MDMA group compared to the placebo group. Several participants reported improved interaction with family members, two reported being able to initiate dating, and two reported feeling more comfortable in expressing and exploring their gender identity. While there were no serious adverse side effects for the MDMA group, moderate elevations in blood pressure, heart rate, and temperature were observed but were mild or brief. In comparison, the mean scores of the placebo group improved near the end of the study, but not to the extent the MDMA group had.


While the study has found rapid and consistent improvement in social anxiety in autistic adults following MDMA-assisted psychotherapy, it is too soon to conclude if MDMA could be used as a treatment for social anxiety because of the small sample size. Although, the study does establish the safety and feasibility of MDMA-assisted psychotherapy. Therefore, more studies with larger sample sizes are needed to further investigate MDMA’s potential. However, like cannabis, MDMA is also a DEA Schedule I drug. Its street drug counterpart, Ecstasy, is often abused and adulterated with methamphetamine or cocaine, making the DEA recognize MDMA itself as a drug with high potential for abuse. As previously stated, supervised pure MDMA use is safe for consumption when taken in limited and moderate doses. Despite not being a cure-all for autism, MDMA’s ability to enhance prosocial behaviors must be further explored as a potential treatment option for social anxiety. Thus, to facilitate more research about MDMA-assisted psychotherapy, changing MDMA’s drug schedule is recommended to receive more funding.

As previously mentioned, cannabis is one of the complementary health approaches (CHAs) that is growing in popularity in the autism community. One CHA, however, has already been commonly used as a treatment for thousands of years: traditional Chinese medicine. Chinese herbal medicine has been used for various health conditions, including, anxiety, gastrointestinal problems, and developmental disorders like autism (Bang et al., 2017). Despite its long history of use, there is a lack of evidence on Chinese herbal medicine’s pharmacological effectiveness because of a lack of clinical studies and western scientific reviews. In an evaluation of multiple studies on Chinese herbal medicine, Bang et al. concluded that herbal medicines together with conventional treatment can have positive results in autistic children. In two of the examined ten studies, it was found that administering herbal medicines combined with conventional therapy for at least three months improved the participants’ Childhood Autism Rating (CARS) scores (Jiang et al., 2016, Zhou, 2015; Bang et al., 2017). However, the diversity and variety of herbal medicines makes it difficult to find the optimal composition of proper herbal medicines and therapy. Bang et al. did find that the most common herbal medicines used were Poria cocos, Panax ginseng, Acorus gramineus, Schisandra chinensis, and Glycyrrhiza uralensis. The commonly used herbal medicines may treat symptoms of inattention, behavioral outbreaks, and inattention (Cai et al., 2015, Bang et al., 2017). A. gramineus is used as a sedative, antispasmodic, and for other pediatric conditions such as cough, epilepsy, abdominal pain, insomnia, and memory loss (Rajput et al., 2014; as cited in Bang et al., 2017). S. chinensis and P. cocos also have sedative, hypnotic, and tonic effects (Zhang et al., 2014, Rios, 2011; as cited in Bang et al., 2017). While herbal medicines help alleviate symptoms, further research is still needed to determine the deeper pharmacological mechanisms of each ingredient when treating autism.

Although there are supposed benefits from taking herbal medicines, there are some disadvantages that make handling and administration cumbersome. For example, herbal medicines are often taken in large doses, perishable, and inconvenient to carry around (Cai et al., 2015). Also, since Chinese herbal medicine is seen as a CHA and is not recognized as a serious form of treatment in western cultures, there are few studies to test its legitimacy. In the east, not many cultures openly talk about autism, which makes Chinese medicine the efficacy on autism not clear. Like CBD and MDMA, there needs to be more interest and research to explore the active ingredients of herbal medicine with the goal of possible prescriptions. Interestingly, unlike CBD, MDMA, and medications intended to treat symptoms of autism, Chinese herbal medicine aims to treat autism as a whole. Traditional Chinese medicine believes that autism occurs in the brain and various organs such as the spleen, heart, and kidney. Thus, herbal medicines have multi-mechanisms to treat multiple symptoms (Cai et al., 2015). It is worthwhile to study Chinese herbal medicine more, especially since it has been established as a CHA and has a history of thousands of years.

Autism spectrum disorder is a lifelong developmental disorder that affects an individual’s communication and behavior. Individuals with autism have difficulty interacting with others and symptoms that can hurt their ability to function in their daily lives. These complications can compromise the quality of life of the autistic individuals and their caregivers. Since each case of autism varies in type and severity, finding the proper treatment plan can be challenging and tedious. The current medications prescribed to treat symptoms – antipsychotics and antidepressants – have adverse effects that can make the patient’s condition worsen. The FDA-approved antipsychotics, risperidone and aripiprazole, have a side effect of weight gain, which is harmful since autistic individuals are already high-risk for obesity. On the other hand, antidepressants may cause diarrhea, insomnia, increased energy, impulsivity, and decreased concentration in patients; this exacerbates many symptoms of autism. Many families can oftentimes feel frustrated when all options are seemingly exhausted. Thus, researching other alternative treatment methods such as CBD, MDMA, and Chinese herbal medicine is valuable and justifiable. Diverging from mainstream treatments may seem risky but, with what is known in the few studies and reviews that are done so far, the results are already promising. CBD has helped several autistic children with their self-injurious behavior and outbreaks, MDMA has made some autistic individuals socially interact more, and Chinese herbal medicine is known to treat a myriad of symptoms from a single concoction. For now, the autism community should be aware of the potential of these alternative medications. If both cannabis and MDMA are recognized as having potential for medicinal use, the DEA will be able to reschedule the drugs and allow more funding to be funneled to research. Chinese herbal medicine, which is also used to treat other conditions other than autism, is critical to examine since it is a popular complementary health alternative. In order to increase the quality of life for those that are affected by autism, looking beyond the medications already known and understanding the optimal types of treatment is imperative.


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