Lysergic acid diethylamide toxicity: Difference between revisions

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==Background==
==Background==
d-lysergic acid diethylamide, more commonly known as LSD, was first synthesized in 1938 by the chemist Albert Hofmann in efforts to chemically create a blood stimulant.<ref>Hofmann A. "Die Geschichte des LSD-25". Triangel Sandoz Zeitschrift fur Medizinische Wissenschaften. 1955;2(3):117-24. (as cited in Ott J. Pharmacotheon. 1993. pg 123.)</ref>In 1943, Hoffman accidently ingested LSD for the first time, discovering its hallucinagenic properties, reportedly seeing "an uninterrupted stream of fantastic pictures, extraordinary shapes with intense, kaleidoscopelike play of colors."
*Also known as d-lysergic acid diethylamide
LSD became very popular in the 1960's and 1970's, making it a very important part of the "counterculture" movement, encouraging participants to  "turn on, tune in, drop out."


==Mechanism==
===Mechanism===
Serotonin like agent
Serotonin-like agents, like LSD, have similar chemical properties of serotonin. These are 5-HT2 agonists, mediating excitatory neurotransmitter release.<ref>Ly, B. "Hallucinogens", ''Rosen's Emergency Medicine: Concepts and Clinical Practice''. 7th Ed. Pgs 2010-2012</ref>  LSD also binds to dopaminergic receptors, contributing to its psychogenic affects.<ref>Marona-Lewicka D, Thisted RA, Nichols DE (2005). "Distinct temporal phases in the behavioral pharmacology of LSD: Dopamine D2 receptor-mediated effects in the rat and implications for psychosis". Psychopharmacology 180 (3): 427–435.</ref>


==Pharmacology==
===Pharmacology===
Known as one of the most potent psychoactive drug, doses of minimum of 25μg. Doses of 1 to 1.5 μg/kg produce psychedelic effects, with the “optimum” dosage for a typical fully unfolded LSD reaction is estimated to be in the range of 100–200 μg.
*Known as one of the most potent psychoactive drug, doses of minimum of 25μg. Doses of 1 to 1.5 μg/kg produce psychedelic effects, with the “optimum” dosage for a typical fully unfolded LSD reaction is estimated to be in the range of 100–200 μg.<br />
*Route of administration can be PO (most common), IM, or IV.<ref>Passie, T. "The Pharmacology of Lysergic Acid Diethylamide: A Review". CNS Neuroscience & Therapeutics, Volume 14, Issue 4,  pages 295–314, Winter 2008</ref>
**PO: Usual Dose 100-250μg, Onset 30-45mins, Peak effect 1-2.5hrs, Total duration 9-12hrs
**IM: Usual Dose 100-250μg, Onset 15-20mins, Peak effect 1hr, Total duration 9-10hrs
**IV: Usual Dose 40-180μg, Onset 3-5mins, Peak effect 1hr, Total duration 9-10hrs<br />
*Tolerance to LSD-25 builds up over consistent use and cross-tolerance has been demonstrated between LSD, [[mescaline]] and [[psilocybin]].<ref>Passie, T. "The Pharmacology of Lysergic Acid Diethylamide: A Review". CNS Neuroscience & Therapeutics, Volume 14, Issue 4, pages 295–314, Winter 2008</ref>


Route of administration can be PO (most common), IM, or IV.  
==Clinical Features==
The acute ingestion of LSD is described as:
"The initial effects begin 20-40 minutes  with a sense of euphoria and dizziness...LSD is best described as a drug that strikes down barriers. The person who uses LSD is likely to feel detached  from his/her ego, and can cross between states of consciousness.  The user's perceptions are altered, causing visual and auditory hallucinations.  One may notice that the walls of room are "breathing" or that motionless curtains appear to be moving.  Senses appear to mix:  a user might see music, taste colors, or hear visual stimuli.  The LSD experience is often difficult to describe by  users -- words lose meaning and are often insufficient in describing the effects of the drug; thoughts may seem unclear.  Effects taper off after about 6-8 hours and are usually completely gone after  a nights sleep."<ref>https://www.erowid.org/chemicals/lsd/lsd_effects1.shtml</ref>


Mode of application Dose (μg) Onset of symptoms (min) Peak effect (h)* Total duration (h)*
"Good Trips" are much like what is described as above, with seemingly normal or usual objects and experiences appearing new and changed to something breath-taking.
Per os 100–250 30–45 1.0–2.5 9–12
Intramuscular 100–250 15–20 1.0 9–10
Intravenous 40–180 3–5 1.0 9–10


The acute psychological effects of LSD last between 6 and 10 h, depending on the dose applied.
"Bad Trips" include experiences of paranoia, acute panic reactions, and agitation, usually stemming from the users prior mood to ingesting LSD. This, along with the user's altered perception of their environment, can lead to the user being subjected to dangers resulting in serious injury, disability, or death.
 
Distribution
 
Tolerance to LSD-25 builds up over consistent use and cross-tolerance has been demonstrated between LSD, mescaline and psilocybin.
 
==Effects==
Trip and what it looks like
Good trip
Bad trip
Medical considerations


==Differential Diagnosis==
==Differential Diagnosis==
===Serotonin-Like Agents===
===Serotonin-Like Agents===
*LSD
*Psilocybin and psilocin dimethyltryptamine (DMT) and 5-methoxy- dimethyltryptamine (5-MeO-DMT)
*Naturally occurring plants like :Hawaiian baby woodrose (Argyreia nervosa), Hawaiian woodrose (Merremia tuberosa), morning glory (Ipomoea violacea), and olili- uqui (Rivea corymbosa)


LSD
===Enactogens===
*Designer amphetamines - [[Bath Salts]], [[Ecstasy]] (MDMA)
*Mescaline (Peyote)


Psilocybin and psilocin dimethyltryptamine (DMT) and 5-methoxy- dimethyltryptamine (5-MeO-DMT)
===Dissociative Agents===
*PCP
*[[Ketamine]]
*Dextromethorphan


Naturally occurring plants like :Hawaiian baby woodrose (Argyreia nervosa), Hawaiian woodrose (Merremia tuberosa), morning glory (Ipomoea violacea), and olili- uqui (Rivea corymbosa)
===Plant-based Hallucinogenics===
*Marijuana
*[[Salvia]]
*Absinthe
*Isoxazole Mushrooms


===Enactogens===
===Psychiatric Illnesses===
Designer amphetamines - [[MDMA]], [[Bath Salts]], [[Ecstasy]]
*[[Schizophrenia]]
*Schizo-affective disorder
*[[Dementia]]
*[[Delirium]]


Mescaline (Peyote)
==Evaluation==
*Usually clinical, based on history and presentation
''Most blood and urine tests are restricted to research and unavailable for clinical usage''


===Dissociative Agents===
===Research Tests===
PCP
*Found in blood specimens (6–12 hours) and urine (2–4 days) after usage
Ketamine
*Metabolite (2-oxo-3-hydroxy-LSD) present in urine for a longer time than LSD itself.<ref>Passie, T. "The Pharmacology of Lysergic Acid Diethylamide: A Review". CNS Neuroscience & Therapeutics, Volume 14, Issue 4, pages 295–314, Winter 2008</ref>
Dextromethotphan
===Plant-based Hallucinogenics===
Marijuana
Salvia
Absinthe
Isoxazole Mushrooms


===Psychiatric Illnesses===
==Management==
Schizophrenia
*Assess for signs of trauma or exposure
Schizo-affective disorder
*Assure patient and staff safety
Dementia
*Agitation:
Delirium
**[[Ativan]] 1-2mg IV, titrate to effect
**[[Haloperidol]] 5-10mg IV, titrate to effect (use as 2nd line agent as may lower [[seizure]] threshold)
''Consider co-ingestions, [[hypoglycemia]], and risk for [[rhabdomyolysis]]<ref>Glaspy, J. "Drugs of Abuse". Emergency Medicine Manual, 6th Ed. Chapt 103, Pgs 502-504.</ref>''


==Workup, Management, and Disposition==
==Disposition==
*Simple LSD ingestion can be safely discharged after a period of observation, once patient has returned to sober baseline and has a safe disposition plan (~4-6 hours)
*Symptoms lasting longer than 8-12hrs can be managed in an observation unit or admitted
**Further work-up and admission is indicated for persistent psychosis or [[altered mental status]],


==See Also==
==See Also==
*[[Hallucinogens]]
*[[Hallucinations]]


==External Links==
==External Links==
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==References==
==References==
<references/>
<references/>
[[Category:Toxicology]]

Revision as of 19:15, 2 September 2019

Background

  • Also known as d-lysergic acid diethylamide

Mechanism

Serotonin-like agents, like LSD, have similar chemical properties of serotonin. These are 5-HT2 agonists, mediating excitatory neurotransmitter release.[1] LSD also binds to dopaminergic receptors, contributing to its psychogenic affects.[2]

Pharmacology

  • Known as one of the most potent psychoactive drug, doses of minimum of 25μg. Doses of 1 to 1.5 μg/kg produce psychedelic effects, with the “optimum” dosage for a typical fully unfolded LSD reaction is estimated to be in the range of 100–200 μg.
  • Route of administration can be PO (most common), IM, or IV.[3]
    • PO: Usual Dose 100-250μg, Onset 30-45mins, Peak effect 1-2.5hrs, Total duration 9-12hrs
    • IM: Usual Dose 100-250μg, Onset 15-20mins, Peak effect 1hr, Total duration 9-10hrs
    • IV: Usual Dose 40-180μg, Onset 3-5mins, Peak effect 1hr, Total duration 9-10hrs
  • Tolerance to LSD-25 builds up over consistent use and cross-tolerance has been demonstrated between LSD, mescaline and psilocybin.[4]

Clinical Features

The acute ingestion of LSD is described as: "The initial effects begin 20-40 minutes with a sense of euphoria and dizziness...LSD is best described as a drug that strikes down barriers. The person who uses LSD is likely to feel detached from his/her ego, and can cross between states of consciousness. The user's perceptions are altered, causing visual and auditory hallucinations. One may notice that the walls of room are "breathing" or that motionless curtains appear to be moving. Senses appear to mix: a user might see music, taste colors, or hear visual stimuli. The LSD experience is often difficult to describe by users -- words lose meaning and are often insufficient in describing the effects of the drug; thoughts may seem unclear. Effects taper off after about 6-8 hours and are usually completely gone after a nights sleep."[5]

"Good Trips" are much like what is described as above, with seemingly normal or usual objects and experiences appearing new and changed to something breath-taking.

"Bad Trips" include experiences of paranoia, acute panic reactions, and agitation, usually stemming from the users prior mood to ingesting LSD. This, along with the user's altered perception of their environment, can lead to the user being subjected to dangers resulting in serious injury, disability, or death.

Differential Diagnosis

Serotonin-Like Agents

  • LSD
  • Psilocybin and psilocin dimethyltryptamine (DMT) and 5-methoxy- dimethyltryptamine (5-MeO-DMT)
  • Naturally occurring plants like :Hawaiian baby woodrose (Argyreia nervosa), Hawaiian woodrose (Merremia tuberosa), morning glory (Ipomoea violacea), and olili- uqui (Rivea corymbosa)

Enactogens

Dissociative Agents

Plant-based Hallucinogenics

  • Marijuana
  • Salvia
  • Absinthe
  • Isoxazole Mushrooms

Psychiatric Illnesses

Evaluation

  • Usually clinical, based on history and presentation

Most blood and urine tests are restricted to research and unavailable for clinical usage

Research Tests

  • Found in blood specimens (6–12 hours) and urine (2–4 days) after usage
  • Metabolite (2-oxo-3-hydroxy-LSD) present in urine for a longer time than LSD itself.[6]

Management

  • Assess for signs of trauma or exposure
  • Assure patient and staff safety
  • Agitation:
    • Ativan 1-2mg IV, titrate to effect
    • Haloperidol 5-10mg IV, titrate to effect (use as 2nd line agent as may lower seizure threshold)

Consider co-ingestions, hypoglycemia, and risk for rhabdomyolysis[7]

Disposition

  • Simple LSD ingestion can be safely discharged after a period of observation, once patient has returned to sober baseline and has a safe disposition plan (~4-6 hours)
  • Symptoms lasting longer than 8-12hrs can be managed in an observation unit or admitted

See Also

External Links

References

  1. Ly, B. "Hallucinogens", Rosen's Emergency Medicine: Concepts and Clinical Practice. 7th Ed. Pgs 2010-2012
  2. Marona-Lewicka D, Thisted RA, Nichols DE (2005). "Distinct temporal phases in the behavioral pharmacology of LSD: Dopamine D2 receptor-mediated effects in the rat and implications for psychosis". Psychopharmacology 180 (3): 427–435.
  3. Passie, T. "The Pharmacology of Lysergic Acid Diethylamide: A Review". CNS Neuroscience & Therapeutics, Volume 14, Issue 4, pages 295–314, Winter 2008
  4. Passie, T. "The Pharmacology of Lysergic Acid Diethylamide: A Review". CNS Neuroscience & Therapeutics, Volume 14, Issue 4, pages 295–314, Winter 2008
  5. https://www.erowid.org/chemicals/lsd/lsd_effects1.shtml
  6. Passie, T. "The Pharmacology of Lysergic Acid Diethylamide: A Review". CNS Neuroscience & Therapeutics, Volume 14, Issue 4, pages 295–314, Winter 2008
  7. Glaspy, J. "Drugs of Abuse". Emergency Medicine Manual, 6th Ed. Chapt 103, Pgs 502-504.