Virtual Reality and Psychedelics for the Treatment of Psychiatric Disease: A Systematic Literature Review

This review (2020) explores the medical applications of Virtual Reality (VR). VR showed security and significant efficacy in the management of disorders like PTSD, gambling disorder and preoperative anxiety, while psychedelics showed positive effects on depressive and anxiety disorders, alcohol use disorder and PTSD. Whether VR and psychedelic therapy could be used simultaneously remains to be seen.

Abstract

“Objective: Hallucinogenic substances or psychedelic drugs have been historically used by humans worldwide for centuries, and interest grows around them because of the therapeutic potential that they pose for mental disease. Virtual Reality (VR), has been highly developed and improved in the last decade, and it is also gaining importance due to their potential as therapeutic tools. In this article, the most recent and relevant information regarding the medical applications of both VR and psychedelics was highlighted, and diverse potential therapeutic uses were explored in hope to set the ground for further research on this topic.

Method: A systematic literature review using the PRISMA methods was conducted in PubMed, Medline, Embase, Cochrane Library, Scopus and Web of Science, including only peer-reviewed clinical trials or case studies written in English, that address the use of psychedelics and/or VR for the treatment of psychiatric disorders and that measure the success of the therapies. A final selection of 23 manuscripts were used in this systematic review.

Results: VR showed security and significant efficacy in the management of special cases of phobias (social, motion pain and spiders), eating disorder, post-traumatic stress disorder (PTSD), gambling disorder, preoperative anxiety and schizophrenia.

Conclusions: The hallucinogenic drugs evaluated exhibited positive effects in treatment of depressive and anxiety disorders, alcohol dependence and PTSD. More research is needed in order to test the effectiveness of these therapies (alone or together) in different mental illnesses and different populations.”

Authors: Federico J. Gómez-Busto & Mario I. Ortiz

Summary

Anxiety disorders

Anxiety disorders are the most commonly found mental disorders, and guidelines have been made for the diagnosis and treatment of panic disorder, agoraphobia, specific phobia, social anxiety disorder, generalized anxiety disorder, PTSD and obsessive-compulsive disorder. Studies have shown that VR based therapies are effective for specific phobias, social phobia, agoraphobia, and PTSD. VRET is more easily accepted by patients than traditional ET, and could be a more accessible, affordable, and potentially exploitable choice for mental health practitioners and patients.

Depressive disorders

Depression is characterized by episodes of diminished mood, disinterest, lack of pleasure, difficulty concentrating, and impairment of sleep and dietary habits, which may affect the quality of life of the individual and eventually lead to suicide.

Eating and weight disorders

The first known immersive simulator dates back to the decade of the 60’s, and was named “Sensorama”. It provided a surrealistic experience with multisensory impressions. In the same decade, Sutherland proposed various ways to program a virtual environment and developed the first “Head Mounted Display” (HMD), preceding the HMD’s that are used nowadays. There are two main types of VR systems: Commercial gaming systems and purpose-designed Virtual Environments.

VR in psychiatry

VR technology has been explored for the treatment of anxiety, depressive disorders, drug dependence, post-traumatic stress disorder, eating disorders, attention deficit hyperactivity disorder, and schizophrenia.

Substance abuse disorders

Studies have been made in order to validate the efficacy of novel VR programs for the diagnosis and treatment of distinct substance abuse disorders, such as alcohol use disorder. These programs include traditional cognitive behavioral therapy (CBT) and relapse prevention training with exposure and coping skill practice in virtual environments.

Schizophrenia

Schizophrenia is a complex chronic mental health disorder with a wide variety of symptoms ranging from delusions and hallucinations to disorganized speech, sometimes causing disability. Non-pharmacological treatment options include meta-cognitive training, narrative therapies, mindfulness therapy, cognitive behavioral therapy, personal therapy and compliance therapy.

VR in other branches of medicine

Studies have shown that VR/AR technologies can be used to reduce pain in different cases, including chronic, acute, related to medical procedures and also in pediatric patients. In addition, VR technologies can be used to improve motor and cognitive function in post-stroke patients.

Hallucinogens and psychiatry

Hallucinogens have been used for thousands of years to treat mental disease, such as anorexia nervosa, bulimia nervosa and binge eating disorder. With the aid of VR technology, patients can alleviate eating-related anxiety and reduce overeating episodes. VR allows the clinician to visualize the patient’s body weight and shape, as well as their triggers and coping abilities, which makes therapy sessions more acceptable to the patient. Therapies targeting the negative self-body image perceptions have been proposed for the treatment of EDs and even obesity. These therapies include a VR-based egocentric-allocentric transformation and supervised cognitive therapy focused on body-image rescripting.

Gender dysphoria

While gender dysphoria (GD) is a complicated condition, it is often treated with cross-sex hormonal treatment or gender reassignment surgery. VR-assisted treatment has not yet focused on GD, but may contribute to develop potential non-invasive VR-assisted treatment options in the future.

Candidates for structured psychotherapy must be carefully selected and prepared, and must not be at risk for the development of psychotic disorders or cardiovascular risk. Ayahuasca is a traditional Amazonian religious-ritual decoction made from the bark of Banisteriopsis caapi, which is rich in beta-carboline harmala alkaloids such as harmaline and harmine. It has been empirically understood and employed by Amazonian populations to heal various psychological or psychosomatic illness.

Substance abuse disorders

Psilocybin has been found to have deep and persisting psychological effects in individuals that consume it, improving behavior, attitude and values, among others. Psychedelics have been tested as an alternative therapy for addiction, with promising results.

Hallucinogens are a diverse group of compounds that have a high affinity for the serotonin 5-HT 2 G-protein coupled receptor and may induce changes in perception, thoughts and emotions, as well as mystical experiences and acute psychosis. Hallucinogenic substances include empathogens, entactogens, dissociative anesthetics, atypical hallucinogens, kappa opioid receptor agonists, ibogaine, anticholinergics, and deliriants. They have a very low probability to cause addiction, but should be used with guidance and appreciation for the powerful psychological effects. Evidence suggests that benzodiazepines may be used for the acceleration of psychotherapy for the treatment of various psychological disorders, and that their physiological effects are less impactful than their psychologic aftermath.

Results

A total of 130 documents were identified through the search in PubMed, Cochrane, Medline, Scopus Embase and Web of Science, and 18 additional records were found through other sources. The results are summarized in tables 1 and 2.

Of the 23 studies assessed in this review, 11 addressed the use of VR-assisted therapies. They focused on specific phobias, eating disorders, PTSD, gambling disorders, preoperative anxiety and schizophrenia.

VR for phobia

In a three-arm randomized controlled trial, VR exposure in CBT for the treatment of Social Anxiety Disorder was investigated. It was demonstrated that VR exposure is more practical and effective than in-vivo exposure. Patients with OCD were exposed to 8 scenarios with the help of an HMD, and a motion tracker, and the results showed that 76.5% of participants had a reliable change from pre to post-treatment.

Studies have shown that LSD and MDMA can be used to treat anxiety-related disorders. Psilocybin and LSD might also be effective, although their inherent psychoactive intensity might make them less ideal than MDMA.

Gender dysphoria

Up to date, no formal research has been made on psychedelics and gender dysphoria, but MDMA has been suggested to improve patients’ health outcomes by decreasing identity threat and increasing access to gender affirmation.

Material and methods

A systematic literature review was conducted using the databases PubMed, Medline, Embase, Cochrane Library, Scopus and Web of Science, with the input of various key words. The results demonstrated that VR-assisted CBT is an effective, efficient and more practical alternative to classical CBT.

In 2016, Gebara et al. used VR to treat social phobia, evaluating 21 subjects with 30) and a Brazilian adaptation of the Dysfunctional Attitude Scale (DAS).

Researchers used a VR headset with 2 Samsung smartphones and a VR application called VIMSE to treat spider phobia. The results showed that both groups experienced strong reductions in symptoms and behavioral avoidance, and non-inferiority was identified after 3 months.

VR for eating disorders

A controlled study was made in Castellón, Spain, to compare the benefits between the use of CBT alone versus CBT with VR for the treatment of EDs. 34 female patients were recruited, with a BMI ranging from 16 to 32 and a range of different symptoms. Regarding the treatment, 15 CBT group sessions and 8 individual psychotherapy sessions with VR techniques were organized in 3 stages: to become aware of body image issues, to change beliefs and attitudes about body and appearance, and to consolidate the achievements of the previous stages.

A study was done using a PC with Windows 7 operating system, polarized passive 3D glasses, a micro-polarized LCD screen with resolution of at least 1,366 x 768 pixels or a 3D TV or monitor, ear headphones for sound immersion, and a keyboard.

A hybrid type 1 implementation-effectiveness study was conducted on 16 veterans with chronic pain syndrome and kinesiophobia. 12 commercially available VR apps were chosen to fit the levels of intensity, starting with low stimulation intensity and moving to high movement intensity. Kinesiophobia was assessed using the Pain Outcomes Questionnaire-VA and the Fear of Daily Activities Questionnaire. Veterans completed 20 minutes of VR during daily physical therapy sessions, and a small effect size improvement was noted for the primary outcome fear of movement.

A parallel-group randomized non-inferiority trial was carried out in Sweden to compare the efficacy of a single session of technician-assisted virtual reality exposure therapy for the treatment of spider phobia.

The results demonstrated that participants with combat-related PTSD decreased by an average of 41.7 points on the Clinician-Administered PTSD Scale (CAPS), and maintained the benefits for as long as six months.

A randomized clinical trial made by Norr, Smolenski & Reger (2018) compared prolonged exposure to visual reality exposure therapy and a wait-list control group in the treatment of PTSD among active duty military personnel. The results showed positive results in regard to symptoms and suicidal ideation.

Preoperative anxiety

In a study made by Dehghan, Jalali & Bashiri (2019), 40 children were placed in front of a computer monitor and experienced the simulated steps of going to an operation room. The results showed that the children had a significant reduction in preoperative anxiety after therapeutic exposure using VRET.

The study measured body image at 3 points: pretreatment, post-treatment and a 1-year follow-up. Patients that received VR-assisted CBT showed greater improvement compared to the only-CBT group, and showed more post-treatment improvement.

Another study addressing eating disorders was conducted by Ferrer-Garcia et al. (2019). 27 patients were randomized to additional cognitive behavioral therapy (A-CBT) and 31 patients were assigned to virtual reality cue-exposure therapy (VR-CET). The results of the study demonstrated a significant reduction in symptomatology in patients who engaged in VR-CET, and this reduction was maintained at the 6-month follow-up.

Post traumatic stress disorder

A randomized controlled trial was conducted on 92 veterans who believed they were suffering from PTSD. The trial examined the effectiveness of trauma management therapy and prolonged exposure therapy.

Patients with auditory verbal hallucinations (AVH) and related beliefs of omnipotence and malevolence created an avatar and used a voice transformer Roland AIRA VT-3 to simulate the voice of the persecutor. The results showed significant improvements in the severity of AVH and related beliefs, while psychiatric symptoms diminished and quality of life improved.

Use of psychedelics

12 papers were reviewed on the use of psychedelics and psychedelic assisted therapies, including five papers on the use of ketamine for different disorders and five papers on the use of psilocybin for alcohol abuse.

Ketamine

In a double blind, controlled, multiple-crossover study with 6-month follow up, 16 patients with treatment-resistant depression in geriatric patients received subcutaneous ketamine HCL in an ascending dose, starting with 0.1 mg/kg and ending with 0.5 mg/kg (according to response). The results showed that ketamine was effective, safe and well tolerated.

Gambling disorders

In a study by Bouchard et al. (2017b), 28 frequent players and 36 occasional players were recruited and played Scrabble, a real video lottery terminal game, a virtual bar with VLTs, and a virtual casino. The results demonstrated that frequent players showed a higher anticipation and desire to gamble. Study 2 addressed the clinical usefulness of a treatment protocol comprising 2 VR immersion sessions for patients with DSM-IV-TR diagnosis of pathological gambling. The results revealed a significant reduction in craving in participants who underwent VR immersion, but no significant difference between groups. 25 adults with DSM-5 criteria for gambling disorders received 4 CBT sessions dedicated to immersion in VR, and the results demonstrated that VR did not induce an urge to gamble.

Schizophrenia

The 7-week phase-II randomized, partial crossover trial by du Sert et al. (2018) compared the effects of VR on schizophrenic patients who were hearing persecutory voices to treatment-as-usual.

Psilocybin

Psilocybin has been widely studied for the treatment of addiction and treatment-resistant depression, and in a study by Bogenschutz et al. (2015), 10 participants with alcohol dependence received a 12-week, 14-session manualized intervention that included two open-label psilocybin sessions.

A clinical trial made by Carhart-Harris et al. (2017) showed that psilocybin has a rapid and sustained antidepressant effect in patients with treatment-resistant major depression.

In another study with psilocybin, 20 patients with treatment-resistant depression received two doses of psilocybin, and the results were significant after a 6 month follow-up.

Griffiths et al. (2016) conducted a randomized 2-session double-blind cross-over trial with 51 cancer patients who received psilocybin on the first session and a low dose on the second session. The participants showed a large, sustained effect on the two primary therapeutic outcome measures.

A randomized controlled trial with crossover design and intranasal administration of ketamine showed significant improvement in depressive symptoms within 24 hours compared to placebo, being well tolerated with almost no psychotomimetic or dissociative side effects or visible hemodynamic changes.

A study was made on 80 patients who were depressed or nondepressed, and the effect of intraoperative sedation of S-ketamine on depression was investigated.

A study was conducted on 27 hospitalized depressive patients on stable antidepressant medication to demonstrate that changes in prefrontal theta cordance 24 hours after a single infusion of ketamine would predict a sustained antidepressant response.

A double-blind clinical trial made by Krupitsky et al. (2002) investigated the effects of ketamine-assisted psychotherapy on heroin addiction. The results demonstrated that the groups that received 75 and 125 mg of MDMA with adjunctive psychotherapy in a controlled setting had significantly greater decreases in PTSD symptom severity.

Discussion

Most studies using VR showed significative efficacy, although some studies had relatively small samples. The most used drugs in the studies with hallucinogens were ketamine and psilocybin.

Our research identified several trials using VR or psychedelics to treat people with psychiatric disorders, including schizophrenia. Unfortunately, not many trials used both.

The studies reviewed were not diverse, and there were no studies focusing on gender dysphoria or OCD, either with VR or psychedelics. The sample sizes were small, and the level of immersion varied depending on the hardware and software used.

Virtual reality and psychedelic assisted therapies were found to be safe and effective, with little or no side-effects during or after the therapy sessions.

14 patients with cancer-related adjustment disorder received single-dose niacin along with psychotherapy. The results showed statistically significant reductions in anxiety and depression at the 6.5 month, first and second follow-up, and 71-100% of participants attributed positive life changes to the psilocybin-assisted therapy experience.

Ayahuasca

A parallel-arm double-blind randomized placebo-controlled trial conducted by Palhano-Fontes et al. (2019) tested the antidepressant action of ayahuasca in patients with treatment-resistant depression. The results reported a rapid antidepressant effect after a single dosing session with ayahuasca when compared with placebo.

3,4-Methylenedioxymethamphetamine (mdma)

In this review, the only study made with the use of MDMA addressed the treatment of PTSD in military veterans, firefighters and police officers. The study showed promising results, but more studies are needed with bigger samples and higher statistical power.

Virtual reality technologies have numerous benefits, both for the clinician and the patient, and the development of software specifically made for therapeutic means needs to be encouraged.

Due to the legal context in many countries, especially developing countries, research with hallucinogens is not easily performed. However, ketamine is a drug that is already used in hospitals, and is not very difficult to obtain.

Although no manuscripts targeting the experimental use of VR and psychedelics along with psychological support were found in our research, we believe that a trial with the use of both methods should be attempted.

Conclusion

VR showed significant efficacy in the management of special cases of phobias, eating disorder, PTSD, gambling disorder, preoperative anxiety and schizophrenia. Hallucinogens produced mild adverse reactions during the studies.