Psychedelics are a class of psychoactive drugs that are known for their ability to produce profound alterations in perception, mood, and cognitive processes, including mystical and spiritual experiences, as well as hallucinations and distortions of sensory perception. The word ‘psychedelic’ is derived from the Greek words ‘psychḗ’ meaning 'soul or mind' and ‘dēleín’ meaning 'to manifest'. Therefore, it literally means "mind manifesting". British psychiatrist Humphry Osmond coined the term ‘psychedelic’ in 1956, suggesting it in a letter to a fellow author - Aldous Huxley.

The word “psychedelic” is a broad umbrella term for a diverse category of natural and synthetic substances. Examples of common psychedelics include:

• Psilocybin (a psycho-active ingredient of “magic mushrooms”)

• LSD (lysergic acid diethylamide)

• MDMA (3,4-methylenedioxymethamphetamine)

• Ketamine

• Ibogaine

• DMT (dimethyltryptamine)

Some psychedelics have been used by Indigenous communities for hundreds or thousands of years. Others were first synthesized in the early 20th century. By the middle of the 20th century, clinicians used psychedelics as adjuncts to psychotherapy, reporting a variety of benefits in treating depression and PTSD. However, in the 1970s they were categorized as schedule I controlled substances, which are said to have “no currently accepted medical use and a high potential for abuse”. This blocked mainstream research on these compounds for decades. Today, numerous psychedelic compounds are studied in laboratories and clinical trials.

Psychedelics have been used by a few indigenous communities for medicinal traditions for millennia. However, the West has been developing our understanding of the pharmacology, physiology and neurology of these substances using the ‘scientific method’ since the turn of the 19th century.

From 1900 to 1950, Swiss, German and American chemists synthesized a wide range of psychedelic substances which we often refer to as ‘Classical Psychedelics’.

From 1950 to 1970, psychedelics went through a burgeoning period of scientific and cultural exploration and were researched extensively in university laboratories and Californian parties.

From 1970 to 1990, the United Nations (UN) Single Convention on Narcotic Drugs and the Convention on Psychotropic Substances, restricted the extent to which these drugs could be researched.

From 1990 to 2010, a ‘Psychedelic Renaissance’ took place, in which pioneers such as Rick Strassman, Franz Vollenweider, David Nutt, and Roland Griffiths, began a resurgence of research into these substances after 20 years of scientific censorship.

From 2010 to today, the interest in psychedelic research has blossomed as new indications are benefiting from psychedelic-assisted psychotherapy. During this time some of the most rigorous studies on psychedelics have been conducted.

To find out more about the history of psychedelics, check out the comprehensive timeline produced by Psychedelic Times.

Psychedelics have shown promise as a therapeutic tool for a variety of mental health conditions as well as neurological disorders. Here are some examples:

Depression and anxiety
Several clinical trials have found that psilocybin can rapidly reduce symptoms of depression in people who do not respond to traditional antidepressant medications. The effects of psilocybin can last for several weeks or months after a single dose. Moreover, psilocybin, MDMA and LSD have both been studied as potential treatments for anxiety disorders, such as social anxiety and PTSD.

End-of-life anxiety
Psychedelics have been studied as a way to alleviate anxiety and improve the quality of life for people with terminal illnesses. Some studies have found that a single dose of psilocybin can significantly reduce anxiety and depression in patients with cancer.

Post-traumatic stress disorder
There is evidence to suggest that psychedelics, such as MDMA and psilocybin, may have therapeutic potential for treating PTSD (Post-Traumatic Stress Disorder). Studies have shown that these substances, when administered in a controlled setting under the guidance of a trained therapist, can help individuals with PTSD process and integrate traumatic experiences, reduce symptoms of anxiety and depression, and improve overall well-being.

Substance use disorders: smoking, alcohol and opioid addiction
There have been some promising results from studies on the use of psychedelics such as psilocybin and LSD to treat addiction to alcohol, nicotine and opioids. One study, for example, found that a single dose of psilocybin was associated with a significant reduction in alcohol use in a small sample of participants with alcohol use disorder. One theory is that psychedelics can help people break free from ingrained thought patterns and behaviors that contribute to addiction. In another research, when 15 smokers took psilocybin two or three times along with cognitive behavioural therapy, 60% dropped the habit 30 months later. Most people saw a substantial reduction in cravings and the emotional aspects of withdrawal — the irritability, fear, and depression — seemed to be better.

Headaches
Psychedelics have shown promise in treating cluster headaches, a type of headache that is often severe and recurring. One study published in the journal Neurology found that psilocybin reduced the frequency and severity of cluster headaches in a group of 53 patients. The effects were long-lasting, with some patients experiencing relief for several weeks or even months after a single dose of psilocybin.

Another study published in the Journal of Headache and Pain reported that LSD, another psychedelic, was effective in treating cluster headaches in a small group of patients. The study found that LSD reduced the frequency and duration of cluster headache attacks.

Anorexia
Anorexia nervosa is the deadliest psychiatric disorder. In a small study published in 2020, researchers found that psilocybin-assisted therapy was associated with significant improvements in eating disorder symptoms, depression, and anxiety among patients with anorexia nervosa. However, this study had a small sample size and lacked a control group, so more research is needed to confirm these findings. A couple of clinical trials with psychedelic compounds are currently underway in this area.

You can browse the full list of ongoing clinical trials alongside indications they address here: Mapping Drug Development in Psychedelics

Psychedelics can induce powerful psychoactive effects such as altered states of consciousness, changes in visual and auditory perception, and altered perception of time and one's own body. The intensity of these effects varies based on factors such as the individual's personality, current state of mind, and surroundings.

Psychedelics have the potential to tap into the innate healing intelligence of the mind and body. They can bring about significant changes in personality, beliefs, and worldview by allowing individuals to step outside themselves and view their habits with fresh eyes. In a supportive environment, these experiences may include feelings of unity and interconnectedness, which can lead to profound insights and personal growth. These experiences are regarded as fundamental to the psychedelic experience. With psychological support, individuals can recalibrate their cognitive and behavioral biases and destructive ruminations.

Psychedelics can allow for a temporary deactivation of mental defences. While this can be immensely beneficial, it can also bring up painful emotions and trauma, resulting in challenging experiences. A skilled facilitator can help mitigate these situations and provide support when needed.

See also: Psychedelic treatments are speeding towards approval — but no one knows how they work. NATURE (01 November 2023)

Activation of serotonin 5-HT2A receptors
While the mechanism of action of psychedelic compounds is not fully understood, it seems that their primary effect comes from the brain’s serotonin 5-HT2A receptors. Psychedelics bind to these serotonin receptors and quieten the Default Mode Network (DMN), which governs our sense of identity. This disrupts the traditional patterns of thinking and enables the activation of new neural pathways. The result is a shift of consciousness and perception. The hypothesis is that activating these receptors allows the brain to remodel old patterns, leading to remission of the symptoms of depression that can last for months after a single psychedelic treatment.

Increased neural connectivity
Another theory is that many psychiatric and neurodegenerative conditions are a result of “cortical atrophy”, the loss of connectivity between the connections of neurons in the pre-frontal cortex. Psychedelics seem to allow these connections to be strengthened and reconnected. The psychedelic state has been compared to the mind of a baby, with billions of synaptic connections yet to be pruned as patterns of thought are established. This altered state of perception and fluid sense of identity have profound implications for mental illness rooted in rigid thought patterns such as depression and anxiety. The patient is able to shift to a different state of awareness, see his/her personality from a role of an observer, see that different ways of thinking and behaving are possible.

Thalamic gating model
There is also a theory called the thalamic gating model. The thalamus is a structure in the brain that takes in sensory information. It is a gate which allows selective information in, so that the rest of the brain is not overloaded. The theory says that psychedelics open up this gate — they remove the gating mechanism and allow a broader perspective.

Neuroplasticity
Psychedelics have been found to have a significant impact on neuroplasticity, which refers to the brain's ability to change and adapt in response to environmental and experiential factors. They seem to increase the growth of new neurons and the formation of new synaptic connections in the brain.
One of the primary ways that psychedelics impact neuroplasticity is by binding to serotonin receptors in the brain, specifically the 5-HT2A receptor. This binding triggers a cascade of molecular and cellular events that ultimately lead to an increase in the expression of certain genes that are associated with neural plasticity.

Direct Binding to BDNF Receptor TrkB

New studies show that psychedelics can help the brain adapt and change by directly connecting with a specific brain receptor called TrkB. This connection boosts the production of a protein called BDNF, which helps new brain connections to form. Interestingly, this process doesn't rely on the usual target of psychedelics, the 5-HT2A receptor, suggesting that psychedelics work in more ways than we thought.
Psychedelics also improve communication between BDNF and TrkB, important parts of the brain's adaptability system. This enhanced communication helps the brain to adapt and contributes to the long-lasting effects of psychedelics.

Reopening of the Social Reward Learning Critical Period
Recent research suggests that psychedelics can "reset" the brain to a more youthful state, allowing it to absorb new information and form important connections between neurons. This process is likened to reopening a "critical period" of learning that typically closes as we mature. In this state, the brain can make long-term changes in behaviour, learning, and sensory systems, which could have significant implications for treating mental health conditions.
The same study found that psychedelics make neurons more sensitive to the hormone oxytocin, which plays a key role in social bonding. This increased sensitivity, referred to as metaplasticity, allows the neurons to rewire and form new connections more readily. This process can be influenced by environmental stimuli, suggesting that the context in which the psychedelic is taken can shape its effects.

Psychedelic-assisted psychotherapy (PAT) is a form of therapy that uses psychedelic substances to facilitate therapeutic breakthroughs and insight. It involves talk therapy and the supervised use of a psychedelic substance to help individuals navigate the experience and integrate insights into their daily life. This combination helps to get to the root of trauma, addiction, depression, anxiety, and other ailments while promoting a renewed sense of purpose and meaning. Psychedelics provide a way to connect pain and healing through participant’s conscious engagement, and they are not an end in themselves.

PAT is completely different from recreational use and involves a rigorous and clinically tested treatment protocol including medical screening, preparation sessions, the treatment day, and integration in a form of psychotherapy sessions.

The exact details of a psychedelic-assisted therapy session can vary depending on the specific substance being used and the therapist's approach. However, there are some general features that are common to most psychedelic-assisted therapy sessions:

Preparation
Before the therapy session, each patient is brought through a medical screening to ensure there are no medical contraindications. Afterwards, the therapist and patient will discuss the patient's goals and expectations for the session during several (usually up to three) preparatory sessions. The therapist will also provide information about the substance being used, its effects, and any potential risks. These preparatory sessions are opportunities for the patient to build trusting relationships with their therapy team, investigate what might come up for them during their treatment day, build on an intention or goal and plan logistics for the treatment day.

Administration of the psychedelic substance
The psychedelic substance is usually administered in a controlled setting, such as a therapist's office or a specialized clinic, with the presence of at least one therapist or facilitator. These psychotherapy sitters are trained to respond to all adverse events that may arise on the day of dosing to ensure patient safety. The patient may ingest the substance orally or through another method such as inhalation.

The psychedelic experience
The patient will usually be lying down or sitting comfortably with their eyes covered and specially prepared music during the psychedelic experience. The therapist will be present to provide emotional support and help the patient navigate the experience. Participants rarely talk and occasionally they might ask for someone to hold their hand. The session may last many hours. During the session, participants are encouraged to explore their experience and go to where it takes them. Often, people go back to places which are challenging, and see the origins of a trauma which led to their depression or PTSD.

Integration
After the psychedelic experience, the therapist and patient will work together to process and integrate the insights gained during the experience into the patient's daily life. This may involve talk therapy during several integration sessions, journaling, and other techniques. Integrating the psychedelic experience into one's life is often the most impactful part of the psychedelic psychotherapy process.

MDMA therapy is different from experiences with classical psychedelics such as LSD or psilocybin. It doesn’t disrupt the consciousness so much and usually, people can talk about their trauma during the session. MDMA is an empathy-booster psychedelic that decreases activity in the amygdala and boosts prefrontal cortex activity. It helps to overcome fear and anxiety when processing trauma. After the treatment session, subsequent psychotherapy sessions can be held. The after-period of neuroplasticity, which may last several weeks, further helps the healing process. The brain is more flexible allowing for better engagement with psychotherapists.

Combination of the drug and therapy, patient’s engagement
Psychedelic-assisted therapy is different from modern pharmaceuticals like antidepressants because it combines pharmacology and therapy. The drugs used in psychedelic therapy are not standalone treatments, but rather a catalyst for a psychotherapeutic process grounded in a relationship-centred approach. This approach considers mental health from a biopsychosocial perspective and encourages patients to actively engage in the recovery process.

Immediate and long-lasting effects with just one or two sessions
Psychedelic therapy offers a significant shift in the treatment of mental health disorders. Rather than masking symptoms with long-term drug intake, it often provides robust clinical benefits with just one or several treatments. Recent studies show that these positive effects can last up to a year. Additionally, unlike current treatments like SSRIs for depression and anxiety, which can take weeks to take effect, psychedelic therapy has an immediate impact.

Studies show that the psychedelic is typically given just once (sometimes twice or three times over a period of weeks) as part of ongoing psychotherapy. This is very different from currently available medications, which are usually given daily and often without much therapeutic support. Despite being the best option available, SSRIs are not very effective and only help about 25 percent of patients who take them.

A different way of working on the brain
Standard antidepressants can help reduce symptoms by suppressing certain brain responses that contribute to depression. This can make it easier to deal with stress, but it doesn't directly address the underlying causes of depression.

Psychedelic therapy takes a different approach. It uses drugs to create a therapeutic state that helps people gain insight and emotional release. With the support of a therapist, this can lead to a healthier outlook and lifestyle. It's more like a direct confrontation with the root causes of mental health problems. During psychedelic therapy, fear is reduced and empathy, trust, and closeness are increased. This, combined with increased brain plasticity, can help people change more quickly. Overall, psychedelic therapy offers a unique way to address mental health issues and may be particularly beneficial for those who haven't found relief from traditional antidepressants.

Feelings, emotions, insights
Psychedelic therapy can have a powerful impact on people's lives, often resulting in a sense of revelation or epiphany. Many report experiencing a shift in perspective and gaining deep insights into themselves and the world around them. They also describe feeling emotionally and physically renewed, with a newfound sense of clarity and balance. In contrast, people who take SSRIs often report feeling emotionally muted, which is quite different from the transformative effects of psychedelic therapy.

It is considered that combining psychedelics with antidepressants such as SSRIs or other medications can be potentially dangerous and should not be attempted without the guidance of a qualified healthcare professional.

However, there is no definite answer or proof confirming such risks, as there hasn’t been enough research conducted so far. A systematic review paper authored by researchers at the Oregon Health & Science University reviewed over three dozen studies to better understand how MDMA and psilocybin interact with other drugs, including antidepressants, beta blockers prescribed for high blood pressure, and other medications. It turns out that many clinical trials for MDMA- or psilocybin-assisted therapy exclude people taking certain drugs, including psychiatric medications. The researchers report that there is a particular lack of research on how psilocybin and psychiatric medications react. Because certain groups, like those with cardiovascular or liver disease, have usually been excluded from clinical trials of psychedelics, it could be a challenge to safely administer psychedelic therapy to those patients since the risks are not yet known.

Research shows that psychedelics are generally physiologically and psychologically safe when delivered in controlled and supportive settings. However, side effects are a fact of life that needs to be accepted, managed in the context of benefits and carefully monitored. Psychedelic treatments, despite being considered generally safe, present real risks, as virtually any effective treatment does. The various compounds used in clinical trials, and in the future – in psychedelic-assisted therapies, have different safety profiles. For example, while psychedelic compounds like psilocybin and LSD are non-toxic and non-habit forming, MDMA can influence blood pressure and ketamine can become addictive over time if not used under strict supervision. As with any other medical treatment, it is crucial to consider the possible benefits and risks and make an informed decision based on that.

To find out more about the safety profiles of specific compounds, see the question What are the main psychedelic compounds and their potential therapeutic applications, effects and risks?

Psychedelics are powerful substances that can produce a range of physical, psychological, and emotional effects. Overall, the risks associated with psychedelics depend on a variety of factors, including the specific substance used, the dose consumed, the individual's physical and psychological health, and the setting in which the drug is consumed. Patients should be informed that these compounds could leave the user vulnerable to emotional, physical or sexual harm, as well as psychiatric complications. These risks are way much higher if the psychedelics are used in a non-medical context, e.g. recreational settings or unsafe environments.

Psychological distress
Psychedelics can cause intense and unpredictable changes in perception, thought, and mood, which can lead to feelings of confusion, anxiety, and paranoia. In some cases, these experiences can trigger underlying mental health conditions or exacerbate existing ones. In very rare cases psychedelics can cause a psychotic reaction. It is more likely among users with a family history of schizophrenia or psychosis; or, if taken with medications that increase serotonin levels, which could cause a dangerous overload. To mitigate these risks, patients should be appropriately screened for pre-existing mental health conditions and properly supervised throughout the duration of their altered state of consciousness as well as in a time following the session.

Physical health risks
Some psychedelics can increase heart rate, blood pressure, and body temperature, which can be dangerous for people with underlying cardiovascular problems. In addition, some psychedelics can cause nausea, vomiting, and other physical symptoms.

Risks associated with unsupervised use
When used outside of a clinical or therapeutic setting, psychedelics can be dangerous, especially if consumed in unknown or unsafe environments and in combination with other substances. Users may be at risk of accidents, injuries, or exposure to harmful substances.

Risk of addiction
While classical psychedelics are not considered to be physically addictive, some people may develop psychological dependence on them and may feel compelled to use them repeatedly.

Sexual abuse risk
Psychedelics induce a specific kind of vulnerability, as they are known to enhance suggestibility and sexual feelings. Many of these substances can leave patients vulnerable to abuse and manipulation by their therapists or guides. While instances of sexual abuse during psychedelic-assisted therapy are relatively rare, they can have devastating consequences for patients and can erode trust in the therapeutic process. Indeed, among all the reports of sexual abuse and ethical misconduct within psychedelic therapies, the concerns being raised are not about the psychedelic substance itself, but about the therapy that is accompanying it. Many survivors of these abuses agree that psychedelics have the potential to be a powerful healing agent but need to be handled with great care and responsibility. Addressing the risk of sexual abuse in psychedelic research and therapy should be adequately prioritized by proper screening and training of therapists and staff, clear guidelines for therapist-patient interactions, monitoring and oversight of the therapists and staff.

Psychedelic substances such as Psilocybin, DMT, LSD, and MDMA are in the Schedule 1 of the United Nations Convention on Psychotropic Substances from 1971. This means that they are considered to lack therapeutic effects and have a high potential for abuse/dependence and to cause serious adverse effects. This scheduling is harmful to scientific research for several reasons:

Restrictions on access
The scheduling of psychedelics as Schedule I drugs has been making it very difficult for researchers to obtain these substances for scientific study. This is because Schedule I drugs are considered to have no medical use and a high potential for abuse, which makes it difficult to obtain the necessary licenses and permits for research.

Limited research funding
Because of the restrictions on access to psychedelic substances, there is limited research funding available to study their potential therapeutic benefits. This means that there are fewer studies being conducted, and those that are being conducted often rely on small sample sizes and limited resources. Before LSD was banned, the US National Institute of Health funded over 130 studies exploring its clinical utility; however, since the ban, it has funded none and until a few years ago, no company was committed to manufacturing medical grade psychedelics and thus procurement of the required drugs for clinical trials was almost impossible.

Biased research
Because of the restrictions on access and funding, the majority of research on psychedelics has been conducted by a small group of researchers who are often associated with a particular institution or organization. This can lead to biased research and a lack of diversity in perspectives and approaches.

Slow progress
The restrictions on access and funding for psychedelic research can slow progress in the development of safe and effective psychedelic-assisted therapies, which could potentially help people suffering from a variety of mental health conditions.

Some of the main challenges include:

Legal and regulatory issues
Psychedelic substances such as psilocybin and MDMA are currently classified as Schedule I drugs, meaning they are considered to have no medical use and a high potential for abuse. This makes it difficult for researchers and clinicians to conduct studies and offer these therapies to patients.

Safety concerns
While psychedelics have been shown to be relatively safe when administered in a controlled setting, they can cause adverse reactions in certain individuals, particularly those with a history of mental illness or cardiovascular problems. Ensuring that patients are properly screened and monitored during treatment is essential.

Standardization of dosing and administration
There is currently no standardized protocol for dosing or administering psychedelic substances, which can make it difficult to compare studies and ensure consistent outcomes.

Integration and aftercare
Psychedelic experiences can be profound and transformative, but they can also be difficult to integrate into everyday life. Ensuring that patients receive adequate support and follow-up care after treatment is essential to maximize the benefits of these therapies.

Access and affordability
Psychedelic-assisted therapies may not be accessible or affordable to all patients, which can limit their potential impact. Addressing issues of accessibility and affordability, including reimbursement by health insurance, is crucial to ensuring that these therapies can reach those who stand to benefit the most.

Stigma and public perception
Psychedelic substances have a long history of being demonized and stigmatized, and there is still significant public resistance to their use in a therapeutic context. The public will need to see psychedelic medicine as real medicine. Clinicians will have to rethink and expand their definition of what an antidepressant is and even how we should be treating depression. Overcoming this stigma and educating the public about the potential benefits of these therapies will be an ongoing challenge.

If you are interested in enrolling on a psychedelic clinical trial, here are two pages where you can find lists of the ongoing clinical trials:

Psychedelic Support

Atlas of Psychedelic Research

Becoming a psychedelic-assisted therapy practitioner typically requires a combination of education, training, and experience. Here are some general steps you can take to become a psychedelic-assisted therapy practitioner:

Obtain a relevant degree
Many psychedelic-assisted therapy practitioners have a background in psychology, counseling, social work, or a related field. Obtaining a degree in one of these fields can provide a strong foundation for working in psychedelic-assisted therapy.

Gain experience in mental health
Experience working in mental health or counselling is often a prerequisite for becoming a psychedelic-assisted therapy practitioner. This may involve working as a counsellor, social worker, or therapist in a clinical setting.

Obtain necessary licenses and certifications
Depending on the local requirements, a practitioner may need to obtain specific licenses or certifications to practice psychedelic-assisted therapy. This may include a license to practice psychotherapy or counseling, or a certification in psychedelic-assisted therapy from a recognized organization.

Keep up with current research and best practices
The field of psychedelic-assisted therapy is constantly evolving, so it is important for practitioners to stay up-to-date on the latest research and best practices in the field. This may involve attending conferences or workshops, reading academic journals, or networking with other practitioners in the field.

Complete specialized training
Specialized training in psychedelic-assisted therapy is also necessary to become a practitioner. This may involve completing a certification program or training course in psychedelic-assisted therapy. See below a list of such training offered by several organizations:

• MAPS

• The California Institute of Integral Studies (CIIS)

• COMPASS Pathways

• Psychedelics Today

• Fluence

• Institute of Psychedelic Therapy

• MIND Foundation

Psilocybin, a compound produced by many species of fungi, is one of the most well-studied psychedelics. To acknowledge its safety record and potential for treating depression more effectively than existing therapies, the Food and Drug Administration in the US designated psilocybin a breakthrough therapy in 2018 and 2019 for treating drug-resistant depression and major depressive disorder.

Therapeutic applications
Psilocybin, typically taken in pill form, has the potential to treat substance use disorders, including alcoholism and nicotine addiction, as well as depression.

What it does
A psilocybin trip can last more than six hours, and some people describe a positive “afterglow” lasting for months. Effects of psilocybin may include:

• Altered perception of reality, such as changes in visual and auditory perception

• Increased emotional and sensory awareness

• Changes in mood, including feelings of euphoria and anxiety

• Altered sense of time and space

• Spiritual experiences and feelings of interconnectedness

• Potential for "bad trips" or experiences of anxiety, paranoia, and confusion.

Risks
Overall, psilocybin has a low risk of toxicity and very low potential for addiction or dependence. In clinical trials, side effects are usually temporary and mild, and though psilocybin experiences are sometimes challenging because they can bring up difficult emotions, participants often report they are among the most meaningful experiences of their lives, producing benefits that frequently last for months.

Some of the potential risks of psilocybin use include:

• Psychological effects: Psilocybin can cause a range of psychological effects, including changes in perception, mood, and thought processes. Some people may experience anxiety, paranoia, or confusion. It can also cause distressing hallucinations or feelings of panic in some patients, especially at high doses.

• Flashbacks: Some people may experience flashbacks or persistent changes in perception and thought processes after using psilocybin.

• Increased risk of accidents: Psilocybin use can impair cognitive and motor functioning, which can increase the risk of accidents and injury.

• Interactions with other substances: Psilocybin can interact with other substances, including prescription medications and over-the-counter drugs, which can increase the risks of adverse effects.

• Medical emergencies: While psilocybin is not known to be toxic or lethal on its own, using too much or combining it with other substances can lead to medical emergencies.

• Risk of emotional instability: People who have a history of mental illness or emotional instability may be at a greater risk of adverse psychological effects from psilocybin use.

For more information on the therapeutic potential of Psilocybin, please visit the Drug Science website.

First synthesized in 1956, ketamine is used today as an anaesthetic by veterinarians and in emergency or combat medicine. The World Health Organization has included it on its Essential Medicines List since 1985. Every ambulance carries it; requiring no oxygen supply and posing no risk of respiratory suppression, it is one of the safest drugs one can receive in a crisis. Because it is the one psychedelic that’s never been illegal, researchers have been able to explore ketamine’s potential as a mental health treatment — and build a case for its use in humans.

Ketamine works differently from other psychedelics. Most psychedelics — like LSD, MDMA and those derived from plants — operate by affecting serotonin receptors, which alter mood and happiness. Ketamine affects a different class of brain receptors that are important for learning and memory. Both kinds of receptors are found in the brain’s prefrontal cortex, which might explain why ketamine and the other psychedelics seem to have similar impacts on mental health.

Therapeutic applications
Many brain disorders — like schizophrenia, depression and anxiety — are characterized by atrophy in the prefrontal cortex. There is strong evidence, though not yet conclusive, that ketamine helps people with psychiatric disorders by promoting regrowth over time in neurons in this area. That could help explain the near-immediate feelings of relief that users report, which is one of the reasons it has been used in the treatment of suicidal patients.

Esketamine, a form of ketamine, showed such promise for treating major depression, often faster than other drugs, that the F.D.A. approved its limited use in early 2019.

What it does
The effects of ketamine can vary depending on the dose, route of administration, and individual factors such as body weight, tolerance, and sensitivity. Some common effects of ketamine include:

• Analgesia: Ketamine can provide pain relief by blocking certain receptors in the brain and spinal cord. Users taking a low dose might feel as though they’re floating or that their body is numb.

• Sedation: Ketamine can cause sedation or anesthesia, which can be useful during surgical procedures or other medical interventions.

• Dissociation: Ketamine can produce a sense of detachment from reality or a feeling of being outside one's body, which is sometimes described as a "K-hole."

• Euphoria: Ketamine can produce feelings of euphoria or a sense of well-being.

• Cognitive impairment: Ketamine can impair cognitive function, including memory, attention, and executive function.

• Hallucinations: Ketamine can cause visual and auditory hallucinations, which can be either pleasant or unpleasant.

• Increased heart rate and blood pressure.

Risks
Like any substance, ketamine use can come with risks and potential side effects. These risks are increased when ketamine is used recreationally or in higher doses than prescribed.

Some of the potential risks of ketamine use include:

• Addiction: Ketamine has the potential to be addictive, especially when used recreationally or in higher doses than prescribed.

• Psychological effects: Ketamine use can cause a range of psychological effects, including hallucinations, delusions, paranoia, and dissociation.

• Physical effects: Ketamine use can also cause a range of physical effects, including increased heart rate, blood pressure, and body temperature, as well as nausea, vomiting, and dizziness.

• Cognitive impairment: Ketamine use can impair cognitive functioning, including memory, attention, and decision-making.

• Respiratory depression: Ketamine can also cause respiratory depression, which can be dangerous or even fatal in high doses.

• Potential for overdose: Using too much ketamine can lead to an overdose, which can cause seizures, coma, or even death.

• Interactions with other substances: Ketamine can interact with other substances, including alcohol, which can increase the risks of adverse effects and overdose.

For more information on the therapeutic potential of Ketamine, please visit the Drug Science website.

LSD (lysergic acid diethylamide), first synthesized in 1938, is a very potent hallucinogen. It is synthetically made from lysergic acid, which is found in ergot, a fungus that grows on rye and other grains. LSD, also known as acid, is a powerful psychedelic substance that can have both potential therapeutic applications and risks.

Therapeutic Applications
Research suggests that LSD may have therapeutic benefits for a range of mental health conditions, including depression, anxiety, and addiction (it’s shown promise for treating alcohol addiction). Some studies have found that LSD assisted therapy can lead to significant reductions in symptoms of depression and anxiety, as well as improvements in mood, well-being, and spiritual experiences. LSD may also have potential applications in end-of-life care, with research suggesting that it may help alleviate anxiety and depression in patients with terminal illnesses.

What it does
LSD is known to affect serotonin receptors in the brain, leading to altered perception, mood, and thought processes. The effects of LSD can be intense and unpredictable, varying widely from person to person. LSD users have reported feelings of bliss during their trip, being able to see sound and having mystical experiences as well as a sense of closeness with others.

Some of the potential effects of LSD may include:

• Altered perception of reality, such as changes in visual and auditory perception

• Heightened sense of creativity and imagination

• Altered sense of time and space

• Emotional and spiritual experiences

Potential for "bad trips" or experiences of anxiety, paranoia, and confusion

Risks
LSD can be potentially risky, particularly if used in high doses or in uncontrolled settings. Some of the potential risks of LSD use may include:

• Anxiety, paranoia, and confusion

• Hallucinations and delusions

• Potential for accidents and injury

• Potential for "flashbacks" or re-experiencing aspects of the trip

• Potential for exacerbation of underlying mental health conditions

• Risk of serotonin syndrome when combined with other substances or medications

For more information on the therapeutic potential of LSD, please visit the Drug Science website.

MDMA (3,4-methylenedioxymethamphetamine) is a synthetic drug that alters mood and perception. It is also known as ecstasy, molly, or XTC, and is classified as a psychoactive drug that produces feelings of increased energy, pleasure, emotional warmth, and distorted sensory and time perception.

MDMA is typically taken orally in pill or tablet form, but can also be crushed and snorted or injected. It is commonly used in social settings such as clubs or parties, but can also be used therapeutically in certain medical contexts.

Therapeutic applications
MDMA has been studied primarily as a treatment for post-traumatic stress disorder (PTSD) leading to significant reductions in PTSD symptoms, such as flashbacks, nightmares, and avoidance behaviors, as well as improvements in mood, interpersonal functioning, and quality of life. MDMA may also have potential applications for treating anxiety, depression, and addiction.

By facilitating a feeling of connection, MDMA can create a strong “therapeutic alliance” between participants and therapists, building a level of trust to help a person feel protected while engaging with intense emotions, memories, and thoughts.

What it does
The effects of MDMA can be intense and last for several hours, with the experience varying widely from person to person and depending on the dose, setting, and mindset of the individual. MDMA is chemically similar to both stimulants and hallucinogens, and it stimulates the release of neurotransmitters such as serotonin, dopamine, and norepinephrine in the brain, which can cause a sense of euphoria and heightened sensory perception.

In the words of one participant, ‘it’s like being in a box full of puppies.’ You can actually feel safe to bring up things that were otherwise very uncomfortable.

Some of the potential effects of MDMA may include:

• Heightened empathy and feelings of connection to others

• Increased sociability and talkativeness

• Positive mood and an increased sense of well-being

• Altered perception of time and space

• Potential for physical sensations, such as heightened touch sensitivity

Risks
MDMA can be potentially risky, particularly if used in high doses or in uncontrolled settings. Some of the potential risks of MDMA use may include:

• Anxiety, paranoia, and confusion

• Overheating and dehydration

• Risk of serotonin syndrome when combined with other substances or medications

• Potential for accidents and injury

• Potential for long-term neurotoxicity with repeated use, meaning damage to nerve cells in the brain

• In extreme cases - lasting kidney and organ damage as well as heart arrhythmias, especially in patients with related pre-existing conditions

• In rare cases - building tolerance to MDMA

For more information on the therapeutic potential of MDMA, please visit the Drug Science website.