HALLUCINOGEN USE DISORDER

HALLUCINOGEN USE DISORDER

is it worth the trip?

Nour ElAttar 200122779 Dr. Robert Formosa

01

INtroduction to hallucinogen use disorder

Also known as hallucinogen persisting perception disorder, it is the recurrence of drug experiences that occur within a few days or even more than a year after drug use.

[1]

A hallucinogen is a psychoactive agent that can cause hallucinations. - Can also cause perceptual anomalies and other substantial changes in thoughts, emotions, and consciousness

• Hallucinogens:

- LSD - Ketamine - MDMA (ecstacy) - PCP - Marijuana

1. Hallucinogens DrugFacts | National Institute on Drug Abuse [Internet]. National Institute on Drug Abuse. 2022 [cited 22 January 2022]. Available from: https://www.drugabuse.gov/publications/drugfacts/hallucinogens

[2]

World Death Rates Due to Drug Addiction

RUSSIA & LIBYA

USA

2ND highest death rate: 8 per 100 thousand

highest death rate: 20 per 100 thousand

2. Ritchie H, Roser M. Opioids, cocaine, cannabis and illicit drugs [Internet]. Our World in Data. 2022 [cited 22 January 2022]. Available from: https://ourworldindata.org/illicit-drug-use

LSD (Lysergic acid diethylamide)

• Hallucinogen, not a stimulant

• Intoxication:

- Hallucinations (visual, auditory) - Depersonalisation - Psychosis - Possible flashbacks - Anxiety and paranoia

• Medical complications:

- Tachycardia - Hypertension

Mechanism of Action

LSD is known to interact with 5-HT receptors to produce agonist or partial antagonist effects on serotonin activity. The exact mechanism remains unknown to this day, however, there have been studies that suggest an increase of brain activity on the right hemisphere, altered thalamic functioning, and increased activity in the paralimbic structures and the frontal cortex; this all leads to the formation of induced visual imageries.

[3]

3. Hwang K, Saadabadi A. Lysergic Acid Diethylamide (LSD) [Internet]. Ncbi.nlm.nih.gov. 2022 [cited 22 January 2022]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK482407/

MDMA (METHYLENEDIOXY-METHAMPHETAMINE)

• A type of amphetamine

- Increase in release of serotonin - Inhibition of serotonin reuptake

• Intoxication:

- Euphoria - Alertness - Bruxism

• Life-threatening effects:

- Tachycardia, hypertension - Hyperthermia, hyponatremia (increased ADH) - Hepatotoxicity - Heatstroke - Death by overhydration

• Withdrawal:

- Crash after withdrawal - Depression, anxiety, loss of attention - Loss of appetite - Fatigue and lethargy - Jaw pain

Mechanism of Action

MoA: Indirect serotonergic agonist - Acts on the serotonin transporter and is transported into the nerve terminal. - This promotes release of serotonin by a process of transporter-mediated exchange. - MDMA interferes with the storage of serotonin within the vesicles and thus increases the amount of serotonin available to be released - This process can lead to significant increases in serotonin available in the synapse.

[4]

4. Department of Health | Pharmacology of MDMA (ecstasy) [Internet]. Www1.health.gov.au. 2022 [cited 22 January 2022]. Available from: https://www1.health.gov.au/internet/publications/publishing.nsf/Content/drugtreat-pubs-modpsy-toc~drugtreat-pubs-modpsy-2~drugtreat-pubs-modpsy-2-3~drugtreat-pubs-modpsy-2-3-pmdm

PCP (Phencyclidine)

• NMDA receptor antagonist in CNS

• Intoxication:

- Stimulant with altered mental status ~ Psychosis with hallucinations ~ Violent and agitated ~ Loss of painful stimuli - Sympathetic stimulation ~ Tachycardia ~ Hypertension ~ Nystagmus ~ Coma & seizures

• Fatalities caused by trauma!

• Treatment:

- Benzodiazepines (depressants) - Haloperidol (anti-psychotic)

Mechanism of Action

- The N-methyl-D-Aspartate receptor is a type of ionotropic receptor that is found on the dendrites of neurons. - It is a major excitatory receptor in the brain. Normal physiological function requires that the activated receptor fluxes positive ions. - PCP enters the ion channel and binds, reversibly, to a site in the channel pore, blocking the flux of positive ions into the cell. - Inhibiting depolarization of neurons and interferes with cognitive and other functions of the nervous system.

[5]

5. Phencyclidine: Uses, Interactions, Mechanism of Action | DrugBank Online [Internet]. Go.drugbank.com. 2022 [cited 22 January 2022]. Available from: https://go.drugbank.com/drugs/DB03575

current available treatments

Long term consequences

[7]

1. LSD:

• HPPD
• Serotonin syndrome
• Triggers drug-induced psychosis
• Persistant hypertension

1. DETOXIFICATION

3. PCP:

• Speech problems
• Weight loss
• Memory loss
• Anxiety and depression
• Suicidal thoughts
• Psychosis

2. COGNITIVE BEHAVIOURAL THERAPY

2. MDMA:

• Hyperthermia
• Heart, liver, or kidney failure
• Aggression
• Memory loss
• Confusion
• Death

[8]

As an evidence-based treatment, CBT helps clients become aware of inaccurate or negative thinking so they can view challenging situations more clearly and respond to them more effectively.

4. Ketamine:

• Bladder ulcers
• Kidney disease

[9]

7. What Are the Long Term Effects of LSD - Healthy Life Recovery [Internet]. Healthy Life Recovery. 2022 [cited 22 January 2022]. Available from: https://healthyliferecovery.com/what-are-the-long-term-effects-of-lsd/

8. [Internet]. 2022 [cited 22 January 2022]. Available from: https://www.addictionpolicy.org/post/breaking-down-hallucinogen-addiction

9. Cognitive Behavioral Therapy (CBT) | Techniques for Addiction [Internet]. DrugAbuse.com. 2022 [cited 22 January 2022]. Available from: https://drugabuse.com/treatment/therapy/cognitive-behavioral/

NEW DIRECTIONS

Alcohol Use Disorder

Promising pharmacotherapies for the treatment of substance use disorders

- Nalmefene - Prazosin

- Memantine - Vigabatrin

Most of the medications are currently under clinical trials

Opioid Use Disorder

- Antalarmin - Lofexidine

- Baclofen - LY379268

Stimulants Use Disorder

- Amphetamines - Bupropion

- Nepicastat - Carvedilol

Hallucinogen Use Disorder

- Amphetamines are counterproductive, specifically for MDMA addiction - Since most of the above-mentioned drugs overlap, there is a possibility for a treatment soon

[10]

A GENERAL IDEA

10. Forray A, Sofuoglu M. Future pharmacological treatments for substance use disorders [Internet]. British journal of clinical pharmacology. Blackwell Publishing Ltd; 2014 [cited 2022Jan22]. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4014020/

CLINICAL TRIALS

Let's take a closer look

[12]

[13]

COMPLETED

[11]

COMPLETED (phase 2)

Failed

Exercise as a Treatment for Stimulant and Methamphetamine Abuse

Pharmacogenetics of Naltrexone for Stimulant and Methamphetamine Abuse

Aripiprazole Use to Reduce Stimulant Dependence

Interventions:

• Drug: Intranasal Methamphetamine

Outcomes:

• The naltrexone group had a significantly higher number of amphetamine-negative urine samples compared with the placebo group
• A significant reduction in craving levels and self-reported consumption of amphetamine in the naltrexone group was reported

Interventions:

• Methamphetamine-dependent patients with a history of psychosis were assigned to receive aripiprazole or placebo for 8 weeks

Outcomes:

• Psychotic symptoms significantly decreased among those on aripiprazole as compared to placebo

Results:

• Aripiprazole was no more effective than placebo in maintaining abstinence from methamphetamine use

Interventions:

• Vigorous Intensity High Dose Exercise
• Health Education Intervention

Outcomes:

• During the 12-week time frame of the study, there was a strict no substance-use policy

Results:

• Longer-term outcomes were not recorded, so results vary

11. Exercise as a Treatment for Substance Use Disorders Protocol - Full Text View - ClinicalTrials.gov [Internet]. Clinicaltrials.gov. 2022 [cited 22 January 2022]. Available from: https://clinicaltrials.gov/ct2/show/NCT01141608?cond=Stimulant+Abuse&draw=2&rank=2

12. Pharmacogenetics of Naltrexone for Stimulant Abuse - Full Text View - ClinicalTrials.gov [Internet]. Clinicaltrials.gov. 2022 [cited 22 January 2022]. Available from: https://clinicaltrials.gov/ct2/show/NCT03226223?cond=Stimulant+Abuse&draw=2&rank=3

13. Sulaiman AH;Gill JS;Said MA;Zainal NZ;Hussein HM;Guan NC; A randomized, placebo-controlled trial of aripiprazole for the treatment of methamphetamine dependence and associated psychosis [Internet]. International journal of psychiatry in clinical practice. U.S. National Library of Medicine; [cited 2022Jan22]. Available from: https://pubmed.ncbi.nlm.nih.gov/22486597/

IMPACT OF NEW TREATMENT

REDUCED DEATH RATES

REDUCED STIGMA

Most addicts do not feel comfortable seeking help

Lower overdose rates and higher recovery from addiction

BETTER UNIVERSITY EXPERIENCE

Decreased incidences among university students

THANK YOU!QUESTIONS?