Individual Substances

Should not be used by people with:

• Certain cardiovascular conditions:
  • Physiologically, ketamine has an indirect, stimulatory effect on the cardiovascular system, leading to increases in heart rate, cardiac output, myocardial oxygen consumption, and blood pressure.
  • Ketamine is contraindicated for people with cardiovascular conditions in which elevations of blood pressure may be detrimental, such as aortic dissection, myocardial infarction, uncontrolled hypertension, or aneurysms.¹
• Active or untreated psychotic disorder: 
  • Can potentially trigger or worsen psychotic symptoms in individuals with conditions such as schizophrenia.²
• History of substance abuse:
  • People with this history may be more susceptible to developing dependence or experience cravings for continued use.
• Pregnancy and Breastfeeding:³
  • Ketamine can cross the placenta and may have potential risks to the developing fetus.
  • Breastfeeding is also generally discouraged while using ketamine due to potential risks to the infant. 

• People taking certain prescription medications including:
  • Monoamine oxidase inhibitors (MAOIs): 
    • Combining MAOIs with ketamine can increase blood pressure and amplify anxiety responses.
  • Central nervous system (CNS) depressants⁴, such as:
    • Benzodiazapines (e.g. Xanax, Klonopin, Valium, Versed, Restoril and Halcion)
    • Barbiturates (e.g. Phenobarbital)
    • Opioids (e.g. Oxycodone, Fentanyl, Codeine, Hydrocodone)
  • Lithium.

Should be considered with caution by people with:

• Anxiety disorders: might experience heightened anxiety or panic attacks during the experience, due to ketamine’s ability to amplify pre-existing anxiety.⁵
• Glaucoma: ketamine can increase intraocular pressure⁶, potentially worsening symptoms in  individuals with glaucoma.

During the experience:

• Physiological Effects:
  • Gastrointestinal distress:
    • Nausea and vomiting are relatively common acute side effects, especially at higher doses.⁷
    • “K-cramps” are more prevalent in frequent users.⁸ 
    • 21% of patients admitted to the emergency room due to ketamine use reported experiencing abdominal pain.⁹
  • Adverse cardiovascular events: in people with conditions sensitive to increases in blood pressure and heart rate.¹⁰
  • Aspiration on vomit while unconscious.
  • Respiratory depression:
    • Transient minimal respiratory depression may exist if the medication is administered too rapidly or at too high a dose.¹¹
• Psychological Effects:
  • Dissociation:
    • Ketamine’s primary effect, a state where you feel detached from your body and surroundings.  These can range from mild perceptual distortions to a profound sense of depersonalization and derealization, sometimes referred to as the “k-hole.” Some individuals find these effects disturbing or frightening.¹²
  • Amnesia and loss of consciousness.
  • Anxiety and Panic: Ketamine can trigger anxiety, fear, and panic attacks in some users, and can amplify pre-existing anxiety, especially at high doses.¹³
  • Psychotic-like symptoms: including hallucinations, delusions and thought disorder, particularly in those with pre-existing vulnerability to psychosis.¹⁴
  • Other psychological effects: confusion, depression, disorientation, dysphoria, flashbacks, unusual thoughts, excitement, irrational behavior, and insomnia.¹⁵
  • There is some emerging evidence of psychological harm when people have powerful ketamine experiences and don’t feel able to let go.¹⁶ 
• Impairment and incapacitation:
  • Impaired judgment and coordination under the influence of ketamine can increase the risk of accidents and injuries, including falls, traffic accidents, and drowning.¹⁷
  • Impaired judgement, and the physical incapacitation that occurs at high doses, can leave users vulnerable to sexual assault.¹⁸ 

After the experience:

• Physical Effects:
  • Bladder dysfunction:
    • Chronic ketamine use can lead to serious damage to the urinary tract, especially inflammation of the bladder, frequency, incontinence, hematuria, and upper tract obstruction.¹⁹ Sometimes called “ketamine bladder,” this causes painful and frequent urination, blood in the urine and can lead to long-term bladder dysfunction.
    • Studies have found that over 25% of regular ketamine users experience urinary tract issues, with severity linked to frequency and dosage.²⁰ 
  • Ketamine use can also cause liver damage, with reports of bile duct dilation, microscopic bile duct injury, and liver fibrosis.²¹  
• Psychological Effects:
  • Cognitive impairment:
    • Chronic ketamine can lead to cognitive deficits, particularly with memory, attention and learning, potentially contributing to long-term functional impairment.²²
  • Schizophrenia-like symptoms: 
    • Chronic ketamine use may be associated with schizophrenia-like symptoms, including hallucinations, delusions, and detachment.²³ 
  • Addiction and dependence:
    • Ketamine can be addictive, and individuals can develop tolerance, meaning that higher doses are required to achieve the desired effect.  This can increase the risk of adverse effects and potentially contribute to dependence. The problem has been particularly studied in China,  where ketamine addiction has been a societal problem.²⁴ 
    • 17% of users met the criteria for dependence in one study.  Frequent users attempting to quit have reported withdrawal symptoms, including cravings and psychological distress.²⁵ 
    • When individuals engage in prolonged, chronic use of ketamine due to addiction, this dramatically raises their risk of psychological and physiological harm.
  • Neurotoxicity: Human and rat studies suggest that ketamine has the potential to produce neurotoxic effects, particularly with chronic use at higher doses.²⁶  

• High Doses
  • Higher doses of ketamine produce more intense psychological and physiological effects than lower doses, which increases all of the acute psychological and physiological risks during the experience.
  • Higher doses increase the likelihood of having experiences that are unpleasant, disturbing, confusing, etc., and are more impairing and incapacitating. 
  • Chronic use of higher doses is associated with greater risks of long-term physiological harms such as bladder dysfunction and psychological harms such as cognitive impairment.²⁷
• Psychological vulnerabilities
  • Individuals with pre-existing mental health conditions, such as personality disorders, may be at increased risk of experiencing adverse psychological reactions.²⁸
• Unsafe environments
  • With classic psychedelics, research has found that unsafe or complex environments increase the chance of a challenging experience and exacerbate psychological distress; this is likely also true with ketamine.
  • In a study of esketamine patient experiences, patients reported that the ideal setting was one that felt safe, warm and comfortable, and in which they did not have to be concerned about being disturbed by other people. Patients often became unsettled and distressed in settings that lacked these features.²⁹
  • Certain physical environments, such as a rooftop or a body of water, can be extremely dangerous in terms of the risk of accidental injury or death. This is especially true when using ketamine in higher doses, which increase dissociation and physical incapacitation, or without supervision by a sober person. The tragic death of actor Matthew Perry is a well-known cautionary tale: he was alone and on a very high dose of ketamine when he drowned in his hot tub.
  • In social environments where the risk of encountering predatory individuals may be heightened, such as party or nightlife settings, the incapacitating effects of ketamine can increase users’ vulnerability to sexual assault.³⁰ 
• Co-administration with other substances
  • Combining with alcohol, benzodiazepines or other CNS depressants can increase the risk of sedation, respiratory depression and even death.³¹
  • Combining ketamine, which can cause nausea, vomiting and even unconsciousness, with substances that also cause nausea, vomiting and sedation greatly increases the risk of aspiration on vomit while unconscious.
  • A study has revealed that ketamine, when combined with other drugs, is a significant contributor to overdoses and fatalities. Specifically, ketamine was found to be involved in 79% of overdose cases and 89.1% of deaths related to co-ingestants.³² 
• Individual sensitivity
  • Responses to ketamine vary considerably between individuals due to genetics, metabolism and prior drug experience.³³
• Lack of standardized protocols
  • This leads to inconsistencies in practice, no clear definition of what constitutes a “low, medium or high” dose and can lead to unintentional adverse effects.³⁴

Should not be used by people:

• With uncontrolled heart conditions such as arrhythmias, coronary artery disease, uncontrolled hypertension, and severe cardiovascular disease.
  • Individuals with severe heart conditions should not use MDMA due to the risk of life-threatening complications ¹. 
• With active Psychotic Disorders: There are case reports of individuals without histories of psychosis experiencingprolonged psychotic symptoms after using MDMA, which suggests that MDMA may exacerbate symptoms in individuals already in active psychosis ².
• With active suicidality: Post-experience depression may raise the risk of suicide ³.
• Who are or may be pregnant: Prenatal MDMA exposure has been linked to poorer infant mental health and motor development ⁴. 
• Who are breastfeeding: MDMA can readily diffuse into breastmilk. Due to potential risks to the infant, MDMA should not be used while breastfeeding ⁵. 
• Taking certain prescription medications including:
  • Concurrent use of monoamine oxidase inhibitors (MAOIs): This is absolutely contraindicated as it can lead to severe and potentially fatal serotonin syndrome ⁶.
  • This risk extends to the use of the reversible MAOI moclobemide for strategic potentiation of MDMA effects, which has been repeatedly documented ⁷.

Only with caution or medical supervision by people with:

• History of seizures: MDMA use can cause seizures, so individuals with a history of seizures should exercise extreme caution ⁸.
• Liver disease: The liver metabolizes and detoxifies MDMA, and it is most vulnerable to the toxic effects of MDMA.  Individuals with liver problems are at elevated risk for hepatotoxicity and other adverse effects ⁹.
• Kidney disease: Many of MDMA’s physiological adverse effects involve or impact the kidneys, so pre-existing kidney issues increase the risk of these adverse effects ¹⁰.
• Mild to moderate cardiovascular issues: Risks can be mitigated with monitoring and medication in clinical settings ¹¹.
• Anxiety disorders: MDMA can potentially exacerbate symptoms of anxiety disorders ¹².
• Depression: Negative moods associated with the recovery period can be more difficult for individuals with depression ¹³.
• PTSD or history of trauma: Since MDMA can facilitate the re-experiencing of traumatic memories, people with histories of trauma may face a higher risk of difficult, distressing experiences and possible extended difficulties ¹⁴.
• Selective serotonin reuptake inhibitors (SSRIs) or other serotonergic medications: SSRIs can increase the risk of serotonin toxicity, necessitating careful medical supervision and potential dose adjustments ¹⁵.

During the trip:

• Somatic and physiological harms: 
  • The most commonly reported include jaw clenching/muscle tension, headaches, nausea, fatigue, and lack of appetite.  Other acute physical side effects include feeling cold, thirst, dizziness, perspiration, restlessness, and somatic pain ¹⁶.
  • MDMA sessions in clinical research are associated with statistically significant, mild and transient increases in blood pressure, body temperature, and heart rate ¹⁷.
    • In non-clinical use in certain circumstances, especially for individuals with vulnerabilities, these increases can escalate into conditions that require treatment and may even result in death ¹⁸.
  • Hyperthermia, which is a dangerously elevated body temperature, can occur due to a combination of pharmacological, behavioral, and environmental factors.
    • Hyperthermia is by far the most common cause of MDMA-related deaths in recreational contexts ¹⁹.
  • Dangerous cardiovascular reactions can occur, primarily in individuals with pre-existing vulnerabilities, due to MDMA’s effects on blood pressure and heart rate.
    • Cardiovascular events are also a common cause of MDMA-related deaths in non-clinical settings ²⁰.
  • Hyponatremia, low sodium ²¹,a complication involving an excessively high ratio of water to sodium in the body, can occur after a single dose of MDMA, and can in severe cases present as a life-threatening condition ²².
    • It is one of the top three most common causes of MDMA-related deaths with illicit use ²³. 
    • In a controlled study, a 37% incidence of hyponatremia was observed in participants with unrestricted fluid intake after a single, safe-range MDMA dose; hyponatremia was not observed in any of the restricted fluid intake participants ²⁴. 
  • Serotonin syndrome:
    • MDMA, primarily in combination with other substances and certain environmental factors, can cause serotonin syndrome ²⁵. Moderate to severe cases require medical treatment and can be life-threatening ²⁶. 
    • Serotonin syndrome can cause hyperthermia and dangerous cardiovascular reactions, among other adverse effects ²⁷.
  • Hepatic toxicity and acute liver injury can occur through accumulation of toxic MDMA metabolites, and as a result of hyperthermia ²⁸.
  • Other adverse effects include seizures, metabolic disturbances, coagulopathy, rhabdomyolysis, renal failure and acute kidney injury, multi-organ failure, and strokes. These are mostly caused by hyperthermia, serotonin syndrome, hyponatremia or combinations of those factors ²⁹.
  • Fatal overdose: While the vast majority of MDMA-related deaths involve additional substances, fatal overdoses do sometimes occur from MDMA alone ³⁰. 
• Psychological harms: 
  • MDMA can produce a variety of adverse, unpleasant, or unwanted psychological responses, including:
    • Agitation, hyperactivity, excessive energy ³¹
    • Mood swings, emotional lability ³²
    • Confusion, difficulty concentrating ³³
    • Impaired memory ³⁴
      • Acute impaired memory could potentially reduce the user’s certainty about the amount of the drug they had previously consumed, which could result in dangerous re-dosing and overdosing ³⁵.
    • Anxiety, panic, paranoia, and fear ³⁶
      • Anxiety (including panic attacks) was the most commonly reported psychological adverse effect in a review of both clinical studies and recreational use ³⁷.
  • MDMA may stimulate the emergence of troubling or painful thoughts, feelings, memories, or other inner material during the experience. This can be distressing or overwhelming at the time, and can lead to lasting psychological difficulties ³⁸. 
    • Some researchers suggest that the re-experiencing of traumatic memories and painful emotions may in some cases be a temporary element of a beneficial therapeutic process in the careful clinical treatment of PTSD ³⁹.
• Relational harms
  • Relational harms are harms that occur within or through interpersonal relationships, dynamics and interactions ⁴⁰.
    • MDMA can promote strong feelings of closeness, intimacy and bonding. It increases the desire to interact and connect with other people, biases socio-emotional perception towards the positive, amplifies responsiveness to friendly faces, and increases feelings of generosity ⁴¹. 
    • MDMA also induces heightened feelings of trust, reduced ability to detect threats and hostility, reduced fear, and reduced defensiveness ⁴².
    • MDMA enhances the enjoyment of human touch, increases the perception of others as being attractive, and is widely reported to increase sexual feelings ⁴³.
  • Together, these effects can distort social interactions, and make MDMA users more vulnerable, which can result in:
    • Forming intense connections with the wrong people, such as an abusive partner, an unrequited love or the therapist or guide administering the MDMA ⁴⁴.
    • Saying or disclosing things to inappropriate others at inappropriate times, potentially leading to regret, rejection or loss ⁴⁵.
    • Sexual risk-taking, engaging in sexual activities with inappropriate others ⁴⁶.
    • Accepting, going along with or being less able to defend oneself against inappropriate, intrusive, predatory, manipulative or exploitative behavior ⁴⁷.
    • Being taken advantage of; this could be sexually, emotionally or financially. Users may become more vulnerable to the testing and crossing of boundaries, seduction, and love-bombing ⁴⁸.
    • Becoming a victim of sexual assault, robbery or another serious crime, as a result of trusting or cooperating with the wrong person.

After the trip

• Physiological harms
  • Lasting complications from kidney or liver injury ⁴⁹
    • Neurotoxicity: there is evidence of neurotoxicity with repeated exposure to high-dose MDMA ⁵⁰.
    • Valvular heart disease (VHD): MDMA has effects on valvular interstitial cells that could create a risk ⁵¹.
      • One study found that 28% of the chronic MDMA users had VHD, while none of the control subjects did, and that the severity of the VHD was correlated with greater lifetime use of MDMA ⁵².
    • Lasting harms from non-fatal overdose:
      • One study of MDMA overdoses found 4 out of the 10 survivors sustained permanent neurological, musculoskeletal, and/or renal issues ⁵³.

• Psychological harms

• High Ambient Temperatures:
  • High temperatures, particularly when combined with sustained physical exertion (such as dancing in a club), exacerbate the risk of hyperthermia and hyponatremia. This is partially due to MDMA’s inhibition of the brain’s temperature regulation center ⁶¹.
• Drinking too much or not enough water:
  • Drinking excessive amounts of water raises the risk of hyponatremia, and drinking too little raises the risk of hyperthermia ⁶².
• High doses:
  • All of the risks of using MDMA, especially the somatic and physiological ones, are heightened with higher doses ⁶³.  
  • Very high doses lead to more extreme adverse physiological effects, especially hyperthermia, which may result in death ⁶⁴.
• Chronic use: Heavy, frequent use of MDMA increases the risk of neurotoxicity, valvular heart disease, and cognitive and memory deficits ⁶⁵.
• Unknown Dose, Purity, and Content:
  • Illicitly acquired MDMA has inconsistent purity and strength, making it difficult to control dosage and increasing the risk of unintended consequences ⁶⁶.
  • Approximately 50% of “Ecstasy” pills are adulterated with substances such as cocaine, amphetamines, or fentanyl ⁶⁷.
• Mixing with other substances:
  • Roughly two-thirds of MDMA/ecstasy-related deaths in England and Wales involve another drug besides alcohol ⁶⁸.
  • Combining MDMA with other stimulants, MAOIs, SSRIs and antiretrovirals like ritonavir can lead to serotonin syndrome, a potentially fatal condition ⁶⁹.
  • Mixing with Alcohol: 81% of ecstasy users consume alcohol at the same time as MDMA, which can exacerbate risks ⁷⁰.
• Pre-existing Conditions: Individuals with high blood pressure, heart disease, epilepsy, liver problems, asthma, or with mental health issues like depression, anxiety, or PTSD are at increased risk of adverse events ⁷¹.
• Set and Setting
  • Negative mindsets and moods may increase the likelihood of negative experiences ⁷².
  • Suboptimal or problematic social and interpersonal settings can result in negative experiences and other adverse outcomes ⁷³.
  • If traumatic emotions or memories surface during the experience outside of a supportive psychotherapeutic setting, the risk of acute distress and lasting psychological disturbance is much higher ⁷⁴. 
  • MDMA use is more likely to result in relational harms in certain types of interpersonal situations, such as in sessions with an unethical therapist, in the company of untrustworthy strangers, or with an emotionally unavailable acquaintance ⁷⁵.

• MDMA-assisted therapy was granted breakthrough status by the FDA in 2017 for the treatment of post-traumatic stress disorder.
  • This designation provides speedier review of a drug for treating a serious illness where early clinical results indicate the drug may be better than other treatments. 
  • The FDA, however, has not yet approved MDMA for this, or any other, purpose. 
• MDMA may promote a sense of connectedness with others and can reportedly lead to states of introspection and personal reflection. MDMA is hypothesized to enhance the therapeutic process by increasing openness to experience, including processing memories of the traumatic experience that led to the onset of PTSD ⁷⁶.
• What about microdosing? 
  • Valvular heart disease is a potential risk of chronic MDMA microdosing ⁷⁷.

• Should not be used by people:
  • With serious cardiovascular conditions, such as cardiovascular disease.¹
  • Who are or may be pregnant.²
  • With active psychotic or manic symptoms, or with a personal or family history of a psychotic disorder or non-psychotic mania.³
  • Who are using monoamine oxidase inhibitors (MAOIs), selective serotonin reuptake inhibitors (SSRIs), or other medications that increase serotonin levels or interfere with its metabolism, due to the risk of serotonin syndrome.⁴
• Should only be used with caution or under medical supervision by people with:
  • A history of anxiety disorders.⁵
  • Epilepsy.
    • Seizures have been reported on DMT.⁶
  • Prior negative psychedelic experiences.  These individuals may be more likely to experience challenging experiences.⁷
  • PTSD or a history of trauma.⁸

During the experience:

• Psychological Effects:
  • Anxiety: Transient anxiety is a frequently reported acute effect, particularly during the onset of drug effects.⁹
  • Bad Trips and Challenging Experiences:
    • Intense, overwhelming psychedelic experiences.¹⁰ 
      • Sometimes, difficult and painful psychedelic experiences may present valuable opportunities for learning, development, and/or therapeutic benefit.¹¹
      • DMT can produce uniquely intense and strange psychedelic experiences when inhaled or injected¹²
    • In one survey, 40% of respondents reported feeling fear during the encounter, and 32% rated their experience as being among the most psychologically challenging in their lives.¹³
  • Hallucinations, delusions, paranoia, and psychotic reactions.¹⁴ 
  • Behavior that is dangerous to oneself or others: The profoundly altered state can in rare cases lead to agitated, aggressive, disinhibited, or even self-harming or suicidal behavior.¹⁵
• Physical Effects:
  • Nausea and Vomiting: Nausea and vomiting are commonly reported adverse effects of DMT, particularly when consumed orally as part of ayahuasca.¹⁶
  • Increased Heart Rate and Blood Pressure.¹⁷ 
  • Transient headache: These are sometimes reported during the onset and after resolution of DMT effects.¹⁸
  • Breathing difficulties and chest pains have also been reported, though they are less frequent.¹⁹
  • Fainting and fits/seizures are rare but have been reported.²⁰
  • Asymptomatic bradycardia (slow heart rate) was observed in one rare case.²¹
  • Serotonin syndrome can occur, primarily when ayahuasca or changa is combined with medications that increase serotonin levels, such as SSRI and MAOI anti-depressants.²²

After the experience:

• Psychological Effects:
  • Adverse experiences can sometimes last more than 24 hours after the acute pharmacological effects of the drug have ended.²³
    • A study found that difficulties following the use of DMT lasted longer compared to other drugs.²⁴
      • 76% or respondents reported extended emotional difficulties
      • 58% reported extended self-perception difficulties
      • 52% reported extended cognitive difficulties, 
      • 50% reported extended “ontological difficulties” (how the person understands reality and existence)
      • 34% reported spiritual difficulties,
      • 26% reported perceptual difficulties.
  • Flashbacks/Reactivations:
    • The prevalence of flashbacks is highly variable across studies, ranging from 15% to 77% of psychedelic users.²⁵
  • Hallucinogen Persisting Perception Disorder (HPPD): 
    • HPPD, characterized by persistent visual disturbances such as geometric hallucinations, false perceptions of movement or intensified colors, can occur following DMT use.²⁶  
    • In one study of psychedelic (including DMT) users who experienced negative effects, 25% reported HPPD symptoms.²⁷
  • Psychotic Symptoms/Disorders: 
    • Cases of psychotic symptoms or disorders have been observed mainly in individuals with pre-existing psychiatric vulnerabilities, a family history of psychosis or when DMT is used with other substances.²⁸  
    • Formal diagnoses of psychotic disorders arising after psychedelic use were low (i.e. 20%) in one sample, but these might be underreported.²⁹
  • Potentially-disruptive or otherwise altered perception:
    • Users may experience derealization, a sensation of losing connection with reality.³⁰
    • Users may experience an “entity encounter” after inhaling DMT.³¹
  • Confusion or uncertainty over what is real.”³²
    • Adverse Events Requiring Professional Support: Approximately 12% of ayahuasca users have reported seeking professional mental health assistance for adverse effects.³³

• High or unknown dosage: 
  • Higher doses.³⁴ 
  • Unknown quantities and purity are significant risk factors due to the illegal status of DMT and lack of quality control, leading to a risk of accidental overdosing and toxicity.³⁵
  • Extreme dosing can indicate reckless behavior or underlying mental health issues.³⁶
  • Route of Administration:
    • Rapid rises in blood concentration due to smoking or vaporizing DMT may contribute to intense drug effects and potential adverse reactions.³⁷
  • Individual Factors:
    • Younger individuals may be at higher risk of adverse reactions.³⁸
    • “Bad Trip” History.³⁹
    • Individuals with a history of substance misuse are more likely to be diagnosed with Hallucinogen Persisting Perception Disorder (HPPD).⁴⁰
  • Contextual Factors:
    • Poor “set and setting” (mindset and environment).⁴¹
      • A poor setting, such as a random club or party with strangers, can make the experience more traumatic.⁴²
    • Use in unsupervised settings or uncontrolled or unsafe environments.⁴³
    • Lack of proper preparation, guidance, and integration, or where trust with the session monitor is low.⁴⁴
  • Drug Interactions:
    • Use of other substances, including other psychedelics or substances of abuse, increases the risk of adverse events, given the potential for drug interactions.⁴⁵
    • Polysubstance use, especially with other stimulants, should be avoided due to the risk of dangerous increases in blood pressure and heart rate.
    • There are case reports of fatal adverse events when DMT is combined with other substances like MDMA or 5-MeO-DMT.⁴⁶  MDMA significantly raises serotonin levels and can lead to serotonin syndrome.
    • Combining DMT with MAOIs or SSRIs, including certain medications and harmala alkaloids found in ayahuasca, can lead to adverse reactions, including a potential risk of serotonin syndrome.⁴⁷
    • Combining DMT with substances containing high levels of tyramine can produce hypertension.⁴⁸

Should not be used by people with:¹

• Uncontrolled heart conditions such as hypertension, cardiac arrhythmias, and serious cardiovascular disease.
  • LSD can increase heart rate, temperature and blood pressure. There is a concern for those at high risk for cardiac events.  
  • There is also concern about valvular heart disease (VHD) with regular use (including microdosing) or excessive use, although no cases have been reported with typical LSD use.² 
• Pregnancy
• Epilepsy
• Active psychotic symptoms or personal or family history of primary psychosis
• Current suicidal thoughts or behaviors³

There are health conditions where the advisability of LSD depends on the specific circumstances:

• History of mental health issues, particularly personality disorders or anxiety disorders, increases the risk of a negative experience.⁴ 
  • In individuals with underlying mental health conditions, such as schizophrenia or bipolar disorder, LSD use can potentially trigger or exacerbate these conditions.⁵ 
  • Careful screening, preparation and support are needed, and LSD should be used with caution.⁶  
• People taking certain prescription medications including:
  • Selective serotonin reuptake inhibitors (SSRIs) or Monoamine oxidase inhibitor (MAOI) antidepressants, which, when combined with higher doses of LSD, can increase the risk of serotonin toxity, a potentially dangerous condition.⁷
  • Concurrent use of lithium, which can increase risk of seizures.⁸

During the experience:

• Psychological Effects:
  • Anxiety, panic and confusion: These are the most common acute adverse reactions. 
    • In one study of emergency medical treatment seekers, 69.6% reported anxiety/panic and 64.7% reported confusion. 
    • Especially at higher doses, LSD can trigger intense anxiety and fear, leading to panic attacks. 
    • These can be distressing and may require professional intervention.⁹ 
  • Paranoia/suspiciousness:  About 49% of emergency medical treatment (EMT) seekers reported paranoia.¹⁰  
  • “Bad trips”:  experienced by a significant number of users.
    • Characterized by frightening illusions/hallucinations, overwhelming anxiety, aggression, depression, confusion and fear.¹¹ 
    • LSD often acts like an amplifier.  Positive thoughts, states, encounters and environments can be heightened to ecstatic realms.  Negative thoughts, anxieties, and encounters can easily devolve into hell realms. 
  • Psychosis-like Experiences, such as hallucinations, delusions, and impaired reality testing. 
  • Agitation:  Around 39.2% of those seeking EMT experienced extreme agitation.¹²  
  • Memory loss: About 28.4% of EMT seekers reported memory loss.¹³  
  • Risky behavior and self-harm: Under the influence of LSD, individuals may experience impaired judgment and engage in risky behaviors, potentially leading to self or others.¹⁴  
  • Suicidal ideas: Depression with suicidal thoughts can occur during an acute reaction.  26% of EMT seekers reported thoughts or acts of self harm.¹⁵ 
• Physiological Effects:
  • Cardiovascular stimulation: LSD can cause moderate increases in heart rate and blood pressure.¹⁶ 
  • Increased body temperature.¹⁷  
  • Other physical symptoms, such as headache, impaired balance, feeling of physical weakness, lack of appetite, and restlessness.  One study of emergency medical treatment (EMT) seekers found extreme sweating (26.5%), difficulty breathing (20.6%), and nausea/vomiting (17.6%).¹⁸ 
  • Duration: Acute effects typically last up to 12 hours.  Some adverse effects usually resolve within 24 hours.¹⁹  

After the experience:

• Confusion or uncertainty over what is real:
  • 42% of respondents in one study experienced “struggles around meaning and the nature of reality.”
  • Another 15% reported experiencing “derealization,” which they described as: “confusion or uncertainty over what was real in the days, weeks or months after a psychedelic experience, sometimes feeling they were in a dream, afterlife, purgatory, a movie, a computer game or fake reality.”²⁰ 
• Persisting negative effects:
  • In one study, 22.5% of LSD and psilocybin users reported at least one negative outcome, with the most common being “mental confusion, memory problems, or racing thoughts.”²¹
  • 6% of users reported difficulties lasting longer than one month.  
• Precipitating mental health issues: In a study focusing on negative outcomes, 37.5% of participants had a psychiatric diagnosis that emerged after their psychedelic experience, and anxiety symptoms arose or worsened in 87%.²²  
• Hallucinogen Persisting Perception Disorder (HPPD):   the recurrence of visual disturbances, such as flashes of light, trails on moving objects, and intensified colors, long after LSD use has ceased.
  • Transient visual distortions have been reported by 40-60% of users.²³  
  • One survey found 44.8% of respondents experienced flashbacks.²⁴  
  • HPPD can last for months or even years, though there also have been reports of these symptoms resolving with treatment.²⁵  
• Functional impairment and potential for self-harm: 
  • A survey of 613 individuals with a history of classic psychedelic use found that 8.9% reported functional impairment lasting longer than a day.
  • 2.6% reported seeking medical, psychiatric or psychological assistance after a distressing psychedelic experience.²⁶  
• Prolonged psychosis.²⁷ In a survey study of individuals who experienced long-term negative psychological responses to psychedelics, 13-16% reported psychotic symptoms.²⁸
• Suicidal risk: A 2021 systematic review found that some studies show an association between psychedelic use and increased suicidal thoughts or behaviors, though others show either no or reduced association.²⁹

• Dosage: both higher amounts and uncertainty about dosage/purity. Most participants in one study who had adverse effects reported either uncertainty about their dose or having taken a higher dose than expected.³⁰
  • Higher doses of LSD are associated with a greater likelihood of adverse events.³¹  
  • Not knowing the dose or purity of LSD can make it difficult to predict and manage the effects, increasing the risk of complications.³²  
  • Illegally manufactured LSD may be contaminated with other substances, such as atropine-like agents.³³  
• Set and setting: the individual’s mindset (“set”) and environment (“setting”) significantly impact the experience.  A poor setting, such as a random club or party with strangers, raises the risk of having a bad trip.³⁴ Unsafe or unsupported environments are potential causal factors for negative responses.³⁵  
• Younger age is associated with negative outcomes and increased risk of negative psychological experiences.
  • One study showed that 53% of participants experiencing negative effects were under age 25.³⁶  
  • Another study found that younger age was associated with higher frequency of seeking out emergency medical treatment (EMT) after taking LSD.³⁷ 
• Individual variability: Reactions to LSD can vary significantly between individuals and even within the same individual at different times. 
• Prior mental health conditions.³⁸ 
• Polysubstance use:  Combining LSD with other substances, especially other serotonergic drugs, can increase the risk of adverse events.³⁹  Specifically, the co-use of lithium and other mood stabilizers was found to be associated with a higher risk of harm.⁴⁰  
• Lack of knowledge or experience.⁴¹

• There are no studies investigating the long-term safety or benefits of microdosing.⁴² There are some concerns that regular use of 5-HT2B receptor agonists, even at low doses, may negatively impact cardiac health.⁴³  
• While microdosing is intended to have minimal hallucinogenic effects, some users do report adverse effects, such as intensified anxiety,⁴⁴ racing thoughts,⁴⁵ reduced focus (8.87%), restlessness and/or fatigue (10.59%)  and mental confusion or memory problems.⁴⁶   In an online study of microdosers, 70% of respondents reported at least one adverse effect.⁴⁷