Researchers are exploring the science of psychedelic drugs as a potential treatment for depression. How effective could they be, and what are the regulatory and legal challenges in their use?
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- Overview skip to link
- Anxiety disorders skip to link
- Treatment options for anxiety disorders skip to link
- Lifestyle factors skip to link
- Psychological treatments (psychotherapy) skip to link
- Pharmacological treatments skip to link
- Psychedelic drugs for anxiety disorders skip to link
- Challenges in undertaking research involving psychedelic drugs skip to link
- Research examples skip to link
- Ongoing research skip to link
Anxiety disorders are a common mental health problem and can be treated with psychological therapies and drugs. Research to date shows that a short course of psychedelic drugs, when combined with psychotherapy, can be as effective as existing treatments in reducing anxiety symptoms, and that this effect can be sustained for months. Clinical trials exploring the role of psychedelics are ongoing.
This is our second article evaluating evidence for the use of psychedelic-assisted therapy to treat mental health conditions, following an article on psychedelics for depressive disorders. We intend to publish a major briefing on psychedelic drugs to treat mental health conditions in 2024.
‘Anxiety disorder’ is an umbrella term for a group of conditions characterised by fear and anxiety, and behavioural disruptions. These symptoms are of such intensity that they cause distress or substantial impairment in several aspects of life, including in personal and family relationships, education and work.
The World Health Organization (WHO) includes the following anxiety disorders in its overview of medical conditions:
- Generalised anxiety disorder (GAD). People experience excessive, uncontrollable worry about various aspects of life.
- Panic disorder. Recurrent, unexpected panic attacks accompanied by intense fear.
- Agoraphobia.Fear or avoidance of situations where escape might be difficult or help unavailable in the event of a panic attack.
- Specific phobia. Intense fear of a specific object, situation or activity.
- Social anxiety disorder. Fear of being negatively judged or evaluated in social situations.
- Obsessive-Compulsive Disorder (OCD) .Presence of obsessions (intrusive and unwanted thoughts) and compulsions (repetitive behaviours)*
The WHO estimates that over 300 million people worldwide live with an anxiety disorder. In the UK, survey data shows that approximately 20% of the population report experiencing a high level of anxiety. GAD is the most commonly diagnosed anxiety disorder; over a lifetime, 1-7% of the population in high-income countries would be expected to be diagnosed.
The social and economic costs of anxiety disorders in the UK are substantial, both for individuals and society. The Office for National Statistics reported that between 2019 and 2023, ‘depression, bad nerves and anxiety’ was the most prevalent health condition amongst those economically inactive because of long-term sickness. Beyond personal impacts, people with anxiety disorders account for a large amount of demand on healthcare. Consultations for GAD increased significantly between 1998 to 2018, and levels of anxiety were reported to increase during the COVID-19 pandemic.
Treatment options for anxiety disorders
Treatments include lifestyle changes (such as physical activity) medication (anti-anxiety drugs), and psychotherapeutic interventions (such as cognitive behavioural therapy). Treatment often involves a combination of options to address individual needs.
Some individuals can make a full recovery. In others, symptoms can persist throughout their life and fluctuate, requiring more intensive periods of treatment at different times.
Whilst studies show little difference in the relative effectiveness of drug and psychotherapy for GAD, there are ongoing concerns about the risk of relapse from these treatments. Psychedelics may provide a longer-term treatment.
Some people can benefit from lifestyle changes to ease mild symptoms or to prevent them worsening, including:
- Physical activity is an effective intervention for managing anxiety. It promotes the release of endorphins, which act as natural mood enhancers.
- Sleep hygiene, the term used to describe the establishment of good sleep habits, can be important for managing anxiety. Poor sleep quality can exacerbate symptoms of anxiety disorders. NICE guidelines emphasise the importance of maintaining a consistent sleep schedule, creating a conducive sleep environment, and avoiding stimulants (such as caffeine) before bedtime.
- Stress management such as mindfulness and relaxation exercises can help individuals manage stressors and alleviate symptoms.
Psychological treatments (psychotherapy)
Psychological interventions are an effective treatment for anxiety disorders. They are recommended as the first-line treatment in preference to medication for GAD.
The NHS uses a ‘stepped care’ approach whereby the least intrusive, most effective intervention is offered first. Psychotherapy can be classed as low intensity, such as guided self-help, or high intensity, such as cognitive behavioural therapy (CBT). High-intensity interventions are usually recommended for more severe symptoms. Treatments include:
- Individual non-facilitated self-help is based on CBT principles and allows the individual to work through online or written materials with minimal input from a therapist. This approach allows individuals to address mental health concerns at their own pace, using information and strategies provided in self-help material without the direct involvement of a therapist or facilitator.
- Individual guided self-help is based in CBT principles and empowers individuals to address mental health concerns independently. Through structured guidance, often in written or digital format, individuals learn evidence-based techniques, cognitive strategies, and self-help interventions tailored to their needs. This method enhances self-awareness and equips individuals with tools to manage and alleviate their mental health challenges.
- Psychoeducation groups offer structured sessions on mental health conditions, treatments and coping strategies. Led by professionals, these groups provide information, foster support, and enhance participants’ understanding of their mental health, empowering them to manage symptoms, make informed decisions, and improve well-being.
- Cognitive Behavioural Therapy (CBT) is an evidence-based psychotherapeutic approach for anxiety disorders. It focuses on identifying and modifying negative thought patterns and behaviours associated with anxiety, promoting healthier coping mechanisms.
- Applied Relaxation Therapy is a systematic technique involving progressive muscle relaxation, helping individuals identify and manage muscle tension associated with anxiety. By learning to relax muscles on cue, individuals can reduce anxiety levels and enhance their ability to cope with stress.
- Exposure Therapy is commonly used for specific phobias and obsessive-compulsive disorder (OCD). Individuals are gradually exposed to feared objects or situations in a controlled manner, helping them desensitise and overcome irrational fears.
This summary focusses primarily on GAD as the most common anxiety disorder. However, drugs not listed here may be recommended for other anxiety disorders.
- Selective Serotonin Reuptake Inhibitors (SSRIs) increase serotonin (a chemical transmitter) levels in the brain, contributing to mood stabilisation. Escitalopram or sertraline are commonly prescribed antidepressants that also effectively treat various anxiety disorders.
- Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs) act on both serotonin and norepinephrine systems, providing a dual mechanism of action. Venlafaxine and duloxetine are used to treat anxiety disorders.
- Benzodiazepines act on a signalling system in the brain and have a sedative effect. Diazepam and lorazepam may be prescribed for short-term relief of acute anxiety symptoms. However, due to the risk of dependence, these drugs are generally recommended for brief periods and are generally unsuitable for long-term use.
- Beta-Blockers block the effects of adrenaline and a related chemical transmitter called noradrenaline that are elevated by stress. Drugs such as propranolol are prescribed to manage physical symptoms of anxiety, such as rapid heartbeat and trembling.
Psychedelic drugs for anxiety disorders
The main classes of psychedelic drugs are described in POST’s article on their use to treat depression.
Evidence from several trials suggests psychedelic-assisted psychotherapy can be as effective as existing treatments for reducing anxiety symptoms.
However, a potential advantage of psychedelic-assisted psychotherapy over other forms of treatment is the evidence that it may reduce symptoms over the long-term. The treatment may also be effective in patients whose symptoms have been considered resistant to existing licensed drugs.
This means individuals may be able to have up to three doses of treatment and possibly not need treatment again for a long time. This contrasts with the current requirement to take medication daily and over long periods.
Challenges in undertaking research involving psychedelic drugs
Generally, psychedelic drugs are tested in combination with psychotherapy. This involves the participant being supervised by a trained psychotherapist who guides them through their experience. This is called psychedelic-assisted psychotherapy (PAP). Researchers are examining whether PAP can be used to treat anxiety disorders that develop alongside, or because of, other illnesses.
To assess the effectiveness of any drug, researchers use a study method to minimise bias called a randomised controlled trial. Study participants are split into two groups: one group receives a drug treatment and the other is a control group that does not. The control group is often still given a treatment that contains none of the drug treatment of interest (a placebo) in order to examine the effect of the drug.
In the context of psychedelic treatment, adhering to this process can be challenging because it may be obvious whether an individual has received either the drug or the placebo. Knowing this can introduce a form of bias that may affect the outcome.
Some earlier studies therefore report findings from ‘open-label’ trials – this is where and researchers and participants may have knowledge about who received treatment. These issues create challenges for researchers, who may have lower confidence in the results of many studies involving psychedelic drugs.
Anxiety associated with cancer, life-threatening and terminal illness
Most studies on PAP for anxiety have focussed on people with anxiety and depression related to experiencing a diagnosis of cancer or other life-threatening or terminal illness.
In total, at least 10 studies with over 400 participants have focussed on evaluating the impact of psychedelics on symptoms of anxiety or ‘existential dread’ in response to a cancer diagnosis – a full summary of these articles is available here. Overall, significant and sustained reductions in anxiety symptoms have been found across several research trials:
- One study examined anxiety in 12 patients with life-threatening diseases. It found that after two doses of LSD, self-reported anxiety symptoms were reduced after 2 and 12 months when compared with a control group receiving a placebo.
- A trial used psilocybin-assisted therapy for 12 patients with advanced-stage cancer and anxiety. The participants had significantly reduced scores of measures of anxiety 1 and 3 months after their second dose. These positive findings were repeated in another trial using a single-dose of psilocybin in 29 individuals with cancer-related anxiety in conjunction with psychotherapy. The effects were sustained when participants were followed up after 7 weeks. After 6.5 months, 60-80% of patients had clinically significant reductions in depression or anxiety, demonstrating the long-lasting nature of PAP.
- A large trial compared a very low dose of psilocybin with a high dose on anxiety and depression in 51 patients with life-threatening cancer diagnoses. The study reported significant reductions in anxiety symptoms both immediately after psilocybin-assisted therapy and six months later, demonstrating the effectiveness of this treatment approach in this patient population. To explore the underlying mechanism, researchers subsequently surveyed over 3,000 individuals who had used psychedelics and people who had had near death experiences. They found similar responses between these groups, indicating psychedelic experiences may fundamentally change one’s attitudes towards death and dying. However, the methods used in this survey means that is difficult to account for any elements of bias, such as some types of people being more likely to choose to participate. This is a common issue across research relying on survey data.
Social anxiety disorder
Social anxiety disorder in individuals with autism spectrum disorder (ASD) has also been studied. One such trial, a small double-blinded placebo-controlled trial, tested the effects of MDMA alongside two 8-hour psychotherapy sessions.
The eight individuals with ASD who received MDMA and psychotherapy reported significantly lower social anxiety symptoms at 6-months compared with participants who received the psychotherapy sessions with placebo.
Anxiety occurring alongside treatment-resistant depression
A research group studying the impact of psilocybin-assisted psychotherapy on 20 individuals with treatment-resistant depression also collected data of the impact of two doses of the drug on symptoms of anxiety. This was an open-label study (which means that researchers and participants have knowledge as to what treatment is given). The participants reported significant reductions in symptoms of anxiety at one-week, 3 months and 6 months after the intervention.
Obsessive compulsive disorder (OCD)
There is a resurgence of interest in psychedelics to treat OCD. Following a series of small reports in the 1980s and 90s, in 2006 a trial in 9 individuals found short-lasting reductions in OCD symptoms after up to four doses of psilocybin. Several additional case reports (small articles focusing on cases in single patients) suggest possible long-term improvement of OCD symptoms following psilocybin-assisted therapy.
There is an ongoing clinical trial assessing the impact of psilocybin on OCD. In the absence of randomised controlled trials, which are ongoing, survey data from 174 individuals with OCD who have used psychedelics suggests there may be some effect on the severity of OCD symptoms.
However, such small trials, individual cases and survey reports should be interpreted with caution until the results of a full clinical trial are published.
There is ongoing research focussed on PAP for the treatment of anxiety disorders. Recently announced research trials include:
- A double-blind placebo-controlled study focused on the impact of psychedelic-assisted psychotherapy for short-term OCD symptoms with follow-up at three months. The study is managed by Yale University.
- In January 2024, the EU announced a €6.5m grant to fund a clinical trial investigating the use of psychedelic-assisted therapy, using psilocybin, to treat psychological distress in people with incurable illnesses that require palliative care. The study involves a consortium of 19 partners and will be coordinated by the University Medical Centre Groningen in the Netherlands.
- Psychedelic drugs to treat depression, POST
- Debate on access to psilocybin treatments – Debate Pack 17 May 2023 Number 2023/0108, House of Commons Library
*OCD has been included in this section of our series on psychedelics and mental health conditions as it is often referred to as an anxiety disorder. However, please note that in the ICD-11 ‘obsessive-compulsive disorders’ are classified as a distinct group of disorders.
POST is grateful to Dr Stephen Naulls, ClinicalResearch Fellow at POST, for researching this briefing. POST would like to thank Professor David Nutt (Director of the Centre for Psychedelic Research, Division of Psychiatry, Imperial College London) and Professor Joanna Neill (Professor of Psychopharmacology, University of Manchester) who acted as external peer reviewers in preparation of this article.
Image by: (© By Khunatorn – stock.adobe.com).
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