Background

Hallucinogens are a class of psychoactive substances that can alter an individual’s perception, thoughts, feelings, and awareness. They are often referred to as psychedelics, psychotomimetics, or entheogens. Hallucinogens have been used in various cultures and settings for thousands of years, primarily for religious, spiritual, and medicinal purposes. These substances induce hallucinations, which are sensory experiences that seem real but are not based on external stimuli. 

Some of the most well-known hallucinogens include: 

• LSD (Lysergic Acid Diethylamide): Discovered in 1938, LSD is a potent synthetic hallucinogenic substance. During the counterculture movement, it gained significant popularity in the 1960s and remains one of the most powerful hallucinogens. 
• Psilocybin (Magic Mushrooms): Found in certain types of mushrooms, psilocybin has been used for centuries in traditional ceremonies and rituals. It is currently being studied for its potential therapeutic effects. 
• DMT (Dimethyltryptamine): DMT is found in various plants and is often consumed through Ayahuasca, a traditional brew used by local tribes in the Amazon region for spiritual and healing purposes. 
• Mescaline (Peyote and San Pedro Cactus): Peyote and San Pedro cacti contain mescaline, used by Native American tribes in ceremonial rituals. 
• MDMA (Ecstasy or Molly): MDMA is classified as an empathogen and entactogen, enhancing feelings of empathy and emotional connection. It has some hallucinogenic properties. 
• Ketamine: Although primarily used as an anesthetic, ketamine also has dissociative and hallucinogenic effects, leading to its recreational use. 
• Salvia divinorum: A potent naturally occurring hallucinogen used in traditional rituals by Mazatec shamans in Mexico. 

Epidemiology

• Prevalence: The prevalence of hallucinogen use varies across regions and populations. In general, hallucinogen use is less common than other drug types, such as alcohol, cannabis, or stimulants. However, there has been an increase in interest and use of hallucinogens in recent years, particularly among young adults. 
• Psychedelic Renaissance: The early 21st century witnessed a resurgence of interest in hallucinogens, sometimes called the “Psychedelic Renaissance.” This movement has led to increased research exploring the therapeutic potential of hallucinogens and a growing acceptance of their use in medical and mental health settings. 
• Medical and Therapeutic Use: As mentioned earlier, there has been a renewed interest in hallucinogens’ medical and therapeutic use. Clinical trials exploring the potential of psilocybin and MDMA in treating mental health conditions have shown promising results, leading to increased attention and support for further research. 
• Hallucinogen-Related Emergencies: While hallucinogens are not associated with the same level of overdose risk as some other drugs, they can still pose risks, especially in uncontrolled or unsupervised settings. There have been cases of hallucinogen-related emergencies, primarily due to unpredictable reactions, acute psychological distress, or accidents during the altered state of consciousness induced by these substances. 
• Psychedelic-Assisted Therapy: The concept of psychedelic-assisted therapy, where a hallucinogen is used with psychotherapy, has gained traction. Research suggests that when administered under controlled conditions and with appropriate support, hallucinogens may have therapeutic benefits for different mental conditions, such as treatment-resistant depression, anxiety, and PTSD. 
• Public Perception: Public perception of hallucinogens has shifted over time. While they were heavily stigmatized during the late 20th century due to associations with counterculture movements and concerns about recreational misuse, there has been a gradual reevaluation of their potential benefits when used responsibly and in therapeutic settings. 

Anatomy

Pathophysiology

The pathophysiology of hallucinogen use involves complex interactions between the drugs and the brain’s neurotransmitter systems. Hallucinogens primarily target the serotonin system, particularly the 5-HT2A receptor subtype, critical in modulating mood, perception, and cognition. Below are some critical aspects of the pathophysiology of hallucinogen use: 

• Serotonin Receptor Activation: Hallucinogens, such as LSD, psilocybin, and DMT, structurally resemble the neurotransmitter serotonin (5-HT). When ingested, these substances bind to and activate specific serotonin receptors with a strong affinity for the 5-HT2A receptor subtype. This activation leads to a cascade of effects within the brain. 
• Increased Glutamate Release: Hallucinogens affect serotonin receptors and modulate glutamate, the brain’s primary excitatory neurotransmitter. This leads to increased glutamate release, particularly in the prefrontal cortex. 
• Disruption of Default Mode Network (DMN): The DMN network of brain regions is active during rest and self-referential thinking. Hallucinogens have been shown to reduce the activity and connectivity of the DMN, leading to alterations in self-awareness and a sense of ego dissolution. 
• Altered Communication Between Brain Regions: Hallucinogens disrupt the regular communication between brain regions, leading to enhanced cross-talk and connectivity in certain areas. This altered brain connectivity is believed to underlie the characteristic changes in perception and sensory experiences reported during hallucinogenic trips. 
• Effects on Brain Regions: Hallucinogens can affect various brain regions, including the visual cortex, thalamus, and limbic system. The visual cortex processes visual information, and hallucinogens can induce vivid and complex visual hallucinations. The thalamus is a relay station in the brain, and its function is altered by hallucinogens, contributing to the distortion of sensory perception. 
• Neuroplasticity and Long-Term Effects: Research suggests that hallucinogens may induce neuroplasticity. This could explain their therapeutic effects in conditions like depression and PTSD, where neuroplasticity plays a role in recovery and resilience. 
• Indirect Dopamine Modulation: While hallucinogens primarily target the serotonin system, some substances, like MDMA, can also lead to increased dopamine release. This contributes to the substance’s empathogenic and stimulant-like effects. 

Etiology

The etiology of hallucinogen use involves various factors contributing to an individual’s decision to use these substances. The reasons behind hallucinogen use can be complex and multifaceted and vary from person to person. Below are some key factors that may contribute to the etiology of hallucinogen use: 

• Curiosity and Exploration: Curiosity about altered states of consciousness and the desire to explore different perceptions of reality can drive some individuals to try hallucinogens. These substances are known for their ability to induce unique and profound experiences, which may appeal to specific individuals. 
• Spiritual and Religious Reasons: Many cultures have used hallucinogens to induce transcendent or mystical experiences in religious and spiritual ceremonies. Some individuals may be drawn to hallucinogens for these purposes, seeking a deeper connection to their spiritual beliefs or a higher power. 
• Countercultural Influence: During the 1960s and 1970s, hallucinogens gained popularity as part of the counterculture movement, which emphasized nonconformity and alternative lifestyles. This cultural influence played a role in promoting the use of hallucinogens as a means of rebellion and self-discovery. 
• Peer Pressure and Social Factors: Peer pressure and social influences can be powerful drivers of drug use, including hallucinogens. People may feel compelled to try hallucinogens if they perceive them as a social norm or if their peers use them. 
• Escapism and Coping Mechanisms: Some individuals may turn to hallucinogens to escape from reality or cope with stress, emotional pain, or difficult life circumstances. The altered states induced by hallucinogens may provide a temporary respite from personal struggles. 
• Availability & Accessibility: The availability and accessibility of hallucinogens can also contribute to their use. Certain hallucinogenic substances may be more prevalent or more accessible to obtain in some regions than other drugs. 
• Media and Pop Culture: Representations of hallucinogen use in movies, music, and other forms of media can influence attitudes and perceptions about these substances. Media portrayals may glamorize or sensationalize the use of hallucinogens, which can potentially influence individuals’ decisions to try them. 

Genetics

Prognostic Factors

Prognostic factors in the context of hallucinogen use refer to variables influencing the outcomes or consequences of using these substances. These factors can affect hallucinogens’ short-term and long-term effects on an individual’s physical and mental health and overall well-being. Some important prognostic factors related to hallucinogen use include: 

• Dosage: The amount of hallucinogen ingested can significantly impact the intensity and duration of the effects. Higher doses may lead to more profound and potentially overwhelming experiences, increasing the risk of adverse reactions or psychological distress. 
• Frequency of Use: Repeated or chronic use of hallucinogens can lead to tolerance, diminishing the desired effects. Frequent use may also increase the risk of developing substance use disorders and exacerbate potential negative consequences. 
• Set and Setting: The “set” refers to the individual’s mindset, emotional state, and expectations before using hallucinogens, while the “setting” refers to the physical and social environment in which the substance is taken. A positive and supportive set and setting can enhance the potential for positive experiences, while negative or stressful circumstances may increase the risk of adverse reactions. 
• Mental Health History: Individuals with mental health issues, such as anxiety, depression, or psychotic disorders, may be more vulnerable to adverse reactions when using hallucinogens. These substances can potentially trigger or exacerbate underlying mental health conditions. 
• Personality Traits: Certain personality traits, such as openness to experiences, can influence how individuals respond to hallucinogens. People with higher levels of openness may be more receptive to the effects and potentially benefit from the introspective or therapeutic aspects of hallucinogenic experiences. 
• Support and Integration: The level of support and integration following a hallucinogenic experience can influence the overall impact on an individual’s life. Supportive and non-judgmental environments that encourage reflection and integration of the experience can contribute to positive outcomes. 
• Polydrug Use: The simultaneous use of multiple substances, including alcohol and other drugs, can interact with hallucinogens and lead to unpredictable and potentially dangerous effects. 
• Personal Motivations: The reasons behind using hallucinogens can affect the overall experience and outcomes. Individuals seeking spiritual or therapeutic insights may approach the experience differently than those seeking purely recreational or escapist purposes. 
• Age and Developmental Stage: The age at which hallucinogens are used can be significant. Adolescents and young adults are susceptible to the effects of these substances due to ongoing brain development and vulnerabilities associated with this developmental stage. 
• Access to Resources and Education: Access to accurate information about hallucinogens, their effects, and potential risks can contribute to safer use and more informed decisions. 

Clinical History

Physical Examination

During a physical examination of an individual who has used hallucinogens, healthcare professionals would typically conduct a comprehensive assessment to evaluate the person’s general health, neurological status, vital signs, and any physical symptoms or signs related to hallucinogen use. The physical examination may include the following components: 

• Vital Signs: Measurement of the individual’s vital signs, including blood pressure, heart rate, respiratory rate, and body temperature. Hallucinogens can affect cardiovascular function, so monitoring vital signs is essential, especially in cases of suspected overdose or adverse reactions. 
• Neurological Examination: The healthcare professional will assess the individual’s neurological status, looking for any abnormalities in motor coordination, reflexes, muscle strength, and sensory perception. Hallucinogens can cause altered mental states, so evaluating neurological function is crucial. 
• Pupillary Examination: The healthcare provider may perform a pupillary examination to check for pupil size, response to light, and symmetry. Hallucinogens can cause pupillary dilation (mydriasis), a characteristic effect. 
• Skin Examination: A thorough skin examination may be conducted to look for any signs of allergic reactions, rash, or injuries that could have occurred during the hallucinogenic experience. 
• Gastrointestinal Assessment: If the individual experienced gastrointestinal symptoms such as nausea or vomiting, the abdomen may be palpated to check for tenderness or other abnormalities. 
• Cardiovascular Assessment: The healthcare provider will listen to the heart and lungs to assess cardiac function and respiratory status. This is important as hallucinogens can affect heart rate and blood pressure. 
• Mental Status Examination: Given the potential for altered mental states with hallucinogen use, a mental status examination may assess the individual’s mood, affect, thought processes, cognition, and orientation to time and place. 
• Assessment of Hydration Status: Individuals who experience vomiting or diarrhea during a hallucinogenic experience may be at risk of dehydration so that healthcare professionals may assess their hydration status. 

Age group

Associated comorbidity

Non-specific signs & symptoms 

• Altered perception 
• Hallucinations 
• Altered sense of time 
• Euphoria 
• Dysphoria 
• Synesthesia 
• Ego dissolution 

• Increases/empathy 
• Anxiety and panic 
• Nausea and vomiting 

    Systemic signs & symptoms 

• Cardiovascular effects 
• Dilated pupils 
• Gastrointestinal disturbances 
• Sweating 
• Tremor 
• Restlessness 
• Increased body temperature 
• Muscle tension 
• Nervous system effects 
• Psychological effects 
• Impaired coordination 

Age Group:  

• Adolescents 
• Young adults 

Associated activity

• Substance use disorders 
• Mental health disorders 
• Spiritual and religious practices 
• Recreational use 
• Psychedelic-Assisted Therapy 
• Exploration and self-discovery 
• Alternative & countercultural movements 

Acuity of presentation

The acuity of presentation refers to the severity or urgency of symptoms when an individual seeks medical attention or assistance. In the context of hallucinogen use, the acuity of the presentation can vary based on several factors, including the specific substance used, the dose, the individual’s physical and mental health, and the setting in which the hallucinogen was taken. 

• Emergency Situations: Sometimes, hallucinogen use can lead to medical emergencies. Individuals experiencing severe distress, panic, or uncontrollable behaviors during a hallucinogenic experience may present to emergency departments seeking immediate medical assistance. 
• Psychiatric Emergencies: Hallucinogens can also precipitate psychiatric emergencies, especially in individuals with pre-existing mental health conditions. Acute psychotic reactions, extreme anxiety, or dissociative states may require urgent psychiatric evaluation and intervention. 
• Non-Emergent Presentations: In less severe cases, individuals may present with non-emergent symptoms related to hallucinogen use. These can include feelings of confusion, residual sensory disturbances, mild anxiety, or difficulty processing the experience. 
• Self-Resolution: For many individuals, the effects of hallucinogens will naturally resolve over time as the substance is metabolized and eliminated from the body. In these cases, individuals may not seek medical attention unless symptoms persist or worsen. 
• Therapeutic Settings: The presentation acuity may differ in the context of psychedelic-assisted therapy. Using hallucinogens in controlled therapeutic settings typically involves trained professionals who guide and support the individual throughout the experience, reducing the likelihood of acute medical or psychiatric emergencies. 
• Post-Trip Integration: After the effects of the hallucinogen have worn off, some individuals may seek support for post-trip integration. This involves processing and making sense of the experience and its potential impact on their emotions, thoughts, and behaviors. 

Differential Diagnoses

• Substance Intoxication: Other intoxicating substances, such as alcohol, cannabis, or stimulants, can produce symptoms that may overlap with hallucinogen use. Differentiating between the specific substances involved can be crucial in providing appropriate care. 
• Mental Health Conditions: Some symptoms experienced during hallucinogen use, such as anxiety, panic, or perceptual disturbances, may also be seen in mental health conditions like generalized anxiety disorder, panic disorder, or schizophrenia. 
• Medical Emergencies: Certain medical conditions, such as seizures, migraines with aura, or acute cardiovascular events, can present symptoms that may initially resemble the effects of hallucinogens. 
• Toxic Reactions or Allergies: In rare cases, individuals may have allergic reactions or toxic responses to substances used as hallucinogens, such as contaminated substances or impurities in the drug. 
• Syncope or Vasovagal Reactions: Some individuals may experience fainting or vasovagal reactions during or after a hallucinogenic experience. 
• Psychiatric Emergencies: Hallucinogen use can trigger acute psychiatric emergencies, such as acute psychosis or mood disturbances, which must be differentiated from primary mental health conditions. 
• Serotonin Syndrome: In situations where multiple serotonergic agents are used concurrently, there is a risk of serotonin syndrome caused by excess serotonin in the brain. 
• Neurological Conditions: In some cases, neurological conditions like migraines, epilepsy, or transient ischemic attacks (TIAs) may present with symptoms that can be confused with hallucinogen effects. 
• Post-Traumatic Stress Reaction: Individuals with intense or challenging hallucinogenic experiences may present symptoms similar to those of post-traumatic stress reactions. 
• Drug Interactions: Hallucinogens can interact with other medications or substances, leading to unexpected effects or interactions. 

Laboratory Studies

Imaging Studies

Procedures

Histologic Findings

Staging

Treatment Paradigm

• The treatment paradigm for individuals who have used hallucinogens and present with adverse reactions or distressing symptoms can vary depending on the severity of the situation and the specific needs of the individual.
• The treatment approach should be tailored to address the hallucinogen’s acute effects and any underlying physical or mental health concerns. 

by Stage

by Modality

Chemotherapy

Radiation Therapy

Surgical Interventions

Hormone Therapy

Immunotherapy

Hyperthermia

Photodynamic Therapy

Stem Cell Transplant

Targeted Therapy

Palliative Care

modification-of-interior-and-surroundings-to-manage-hallucinogen-use

• Safe and Calm Setting: Providing a safe and calm environment is essential for individuals with difficult hallucinogenic experiences. A quiet, private space with minimal external stimuli can help reduce feelings of overwhelm and provide a sense of security. 
• Comfort and Familiarity: Surrounding the individual with familiar and comforting objects, such as personal belongings or familiar music, can help anchor them to the present moment and reduce feelings of disconnection. 
• Nature and Natural Elements: A natural setting, such as a garden or park, can be calming and grounding. Nature can help individuals feel more connected to their surroundings and foster a sense of tranquility. 
• Dim Lighting: Soft and dim lighting can create a soothing ambiance and minimize sensory overload, especially for individuals still sensitive to bright lights after their hallucinogenic experience. 

modification-of-surrounding-psychological-aspects-to-manage-hallucinogen-use

• Positive Distractions: Positive distractions, such as calming music, gentle activities like drawing or coloring, or watching relaxing videos, can help shift the individual’s focus away from distressing thoughts. 
• Psychedelic Integration Therapy: For individuals who have undergone significant or challenging hallucinogenic experiences, psychedelic integration therapy can be invaluable. This therapy involves working with a trained therapist to process and integrate the insights and emotions from the experience, promoting healing and growth. 
• Follow-Up Care and Integration Sessions: Follow-up and integration sessions can be beneficial to check on the individual’s well-being and provide ongoing support as they process their experiences. 
• Education on Hallucinogen Use and Safety: Providing accurate and evidence-based education about hallucinogen use and safety can help individuals make informed decisions and reduce potential risks associated with future use. 

Administration of benzodiazepines for the treatment of hallucination use

• Diazepam 
• The use of diazepam (Valium) for the treatment of hallucinogen use is generally limited to specific scenarios where it may be deemed necessary to address acute distress, agitation, or anxiety associated with hallucinogenic experiences. Diazepam belongs to the benzodiazepine class of medications, and its primary effects include sedation, muscle relaxation, and anxiolytic (anti-anxiety) properties. 
• Lorazepam 
• Lorazepam is a benzodiazepine medication commonly used to treat anxiety. It can help alleviate symptoms such as agitation and anxiety associated with acute hallucinogen intoxication or a “bad trip.” However, using benzodiazepines like lorazepam to manage hallucinogen-induced distress should only be done under a medical professional’s supervision. It should not be seen as a primary treatment for hallucinogen use or related disorders. 

Administration of neuroleptics for the treatment of hallucination use

• Haloperidol 
• Haloperidol is an antipsychotic medication sometimes used to manage severe agitation, psychosis, or behavioral disturbances caused by hallucinogen use. Hallucinogens like LSD, psilocybin, or mescaline can induce intense and unpredictable psychological effects. Individuals may sometimes experience severe anxiety, panic, or agitation during a hallucinogenic experience (“bad trip”). 
• Healthcare professionals can prescribe haloperidol in a controlled setting to help manage acute symptoms related to hallucinogen intoxication. It works by blocking dopamine receptors in the brain, which can help reduce agitation and psychotic symptoms.

Administration of antidotes for the treatment of hallucinogen use

• Dextrose 

A dextrose is a form of glucose, a simple sugar that serves as an energy source for the body. It is commonly used in medical settings to raise blood sugar levels in cases of hypoglycemia (low blood sugar) or to provide quick energy to individuals unable to eat or drink. 

Hallucinogen use, such as LSD, psilocybin, or mescaline, involves ingesting substances that can cause altered perceptions and hallucinations. The treatment for hallucinogen use disorder typically focuses on psychological interventions, counseling, and behavioral therapies rather than medical interventions like dextrose. 

During a hallucinogenic experience, individuals may be more prone to experiencing intense emotions, anxiety, or panic. In such cases, medical professionals may use sedatives or benzodiazepines to help manage acute symptoms, but dextrose is not indicated. 

• Thiamine 

Thiamine, also known as vitamin B1, plays a crucial role in the body’s metabolism of carbohydrates and in maintaining proper nerve function. It is commonly used as a supplement to address deficiencies and supports overall health. In the context of hallucinogen use, thiamine may be considered part of a comprehensive treatment plan, especially if an individual is experiencing specific symptoms or complications related to substance use. 

Hallucinogen use, particularly substances like ecstasy (MDMA) and certain synthetic hallucinogens, can sometimes lead to adverse effects that impact brain function, including changes in neurotransmitter activity and potential damage to nerve cells. Thiamine is essential for proper nerve function, and its deficiency can lead to a condition known as Wernicke-Korsakoff syndrome, characterized by confusion, memory problems, and neurological deficits. 

• Naloxone 

Naloxone is an opioid receptor antagonist commonly used to reverse opioid overdose rapidly. On binding with opioid receptors in the brain and blocking the effects of opioids, it helps to restore consciousness and regular breathing in individuals experiencing opioid overdose. 

• Assessment and Evaluation: Before any treatment can begin, a an extensive assessment is conducted to determine the extent of the individual’s hallucinogen use, any co-occurring mental health disorders, and overall physical health. This helps in tailoring the treatment plan to the individual’s needs. 
• Detoxification (if necessary): For individuals with severe hallucinogen use disorders, a detoxification process may be necessary to manage withdrawal symptoms and ensure the individual’s safety. This is often done under medical supervision. 

Counseling and Therapy 

• Cognitive Behavioral Therapy (CBT): This therapy helps individuals identify and change unhealthy thought patterns and behaviors related to drug use. 
• Motivational Enhancement Therapy: This therapy focuses on enhancing an individual’s motivation to change their behavior and engage in treatment. 
• Contingency Management: This involves providing incentives for positive behaviors, such as clean drug tests or attendance in therapy sessions. 
• Psychotherapy: Individual or group therapy sessions can help individuals explore the underlying reasons for their drug use and develop healthier coping mechanisms. 
• Medication-Assisted Treatment (MAT): While there isn’t a specific medication approved for treating hallucinogen use disorders, certain medications might be used to manage withdrawal symptoms, cravings, and co-occurring mental health conditions, if present. 
• Support Groups: Participating in support groups, such as 12-step programs like Narcotics Anonymous (NA), can provide individuals with a sense of community and shared experiences. 
• Education: Providing individuals with information about the effects of hallucinogens and the potential consequences of continued use can be an essential part of the treatment process. 
• Relapse Prevention Strategies: Teaching individuals strategies to identify triggers and develop coping skills to prevent relapse is crucial for long-term recovery. 
• Holistic Approaches: Some treatment programs incorporate holistic approaches such as mindfulness meditation, yoga, and art therapy to promote overall well-being and stress reduction. 
• Aftercare Planning: As treatment progresses, a plan for ongoing support and follow-up care is essential to maintain the progress made in treatment. 

use-of-phases-to-manage-hallucinogen-use

Managing hallucinogen use disorders typically involves several phases to address the individual’s needs and challenges throughout their recovery journey. Remember that the specifics of each phase can vary based on the individual’s circumstances, treatment facility, and the severity of the disorder.  

Assessment and Intake: 

• The initial phase involves a comprehensive assessment of the individual’s history of hallucinogen use, medical and psychological health, social support, and other relevant factors. 
• The assessment helps determine the appropriate level of care and create an individualized treatment plan. 

Detoxification (if necessary): 

• For individuals with severe hallucinogen use disorders, medical detoxification may be needed to manage withdrawal symptoms. Medical professionals typically supervise this phase to ensure safety and comfort. 

Therapeutic Interventions: 

• Counseling and therapy play a central role in addressing hallucinogen use disorders’ psychological and behavioral aspects. 
• Cognitive Behavioral Therapy (CBT), Motivational Enhancement Therapy, and other evidence-based therapies are often used to help individuals understand their triggers, develop coping skills, and make healthier choices. 

Medication-Assisted Treatment (MAT): 

• While no specific medication is approved for treating hallucinogen use disorders, certain medications might be used to manage co-occurring mental health conditions, cravings, or withdrawal symptoms from other substances. 

Relapse Prevention: 

• Individuals learn to identify triggers, develop strategies to manage cravings and build resilience against relapse. 

Continuing Care and Aftercare: 

• Develop a plan for ongoing support and relapse prevention after the initial treatment phase. 
• Engaging in regular follow-up appointments, therapy sessions, and support group meetings. 

Reintegration and Recovery Maintenance: 

• Assisting the individual in reintegrating into daily life, work, and social activities. 
• Focusing on sustaining recovery and promoting overall well-being. 

Medication

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References

• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6887552/ 
• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7943545/ 
• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2648386/