Prescription Medication Misuse

Novel Psychoactive Substances and Prescription Medication Misuse

  • Speaker: Professor Fabrizio Schifano, MD, FRCPsych

    • Affiliation: Psychopharmacology, Drug Misuse and Novel Psychoactive Substances Research Unit, University of Hertfordshire, Hatfield, UK.

Cannabis and Psychopharmacology

  • THC (Tetrahydrocannabinol):

    • Receptor interactions, particularly with the CB1 (Cannabinoid receptor type 1).

    • Endogenous Ligands:

    • Anandamide

    • 2-Arachidonoylglycerol

    • Palmitoylethanolamide

    • Location: Post-synaptic membrane, involved in inhibitory G-protein signaling in the cytoplasm.

Medicinal Ketamine and Urinary Dysfunction

  • Question: Is medicinal ketamine associated with urinary dysfunction issues?

  • Study Analysis:

    • Reviewed reports from the European Medicines Agency (EMA) and UK Yellow Card Scheme (YCS) (Schifano et al., 2020).

    • Ketamine prescribing for psychopathological conditions is increasing.

    • Findings:

    • Out of 9,971 Adverse Drug Reactions (ADRs) reported from 2005-2017:

      • 1,758 ADRs (17.7%) referred to renal/urinary disorders:

      • Kidney/Ureter: 922 ADRs

      • Bladder/Urethra: 837 ADRs

      • Ketamine was the sole drug in 156 out of 194 cases (80.4%).

    • ADRs occurring within 1 month-1 year of ketamine treatment, with 30 cases reported within 48 hours.

    • YCS data correlating with EMA results showed 50 out of 217 ADRs (23%) related to renal/urinary disorders.

    • The current data may grossly underestimate the prevalence of Ketamine Associated Urinary Dysfunction (KAUD).

    • Recommendation: Restrict chronic treatment involving higher doses of ketamine to controlled trials or clinical audits until safety is established.

Prescription Drug Diversion and Misuse

  • Context of Misuse in New Psychoactive Substances (NPS):

    • Terms: "Pharming"; "pharm parties"; "chill pill"

    • Pharmaceutical Drugs Commonly Misused:

      • Gabapentin and Pregabalin

      • Antidepressants:

      • Venlafaxine

      • Bupropion

      • Antipsychotics:

      • Quetiapine

      • Olanzapine

      • Synthetic Opiates/Opioids (e.g., Fentanyl derivatives)

      • Z-drugs:

      • Zaleplon, Zolpidem, Zopiclone

      • Designer Benzodiazepines (e.g., clonazolam, etizolam)

Case Studies and Review Articles

  • Multiple publications by Schifano and Chiappini highlighting misuse potential and adverse effects of:

    • Gabapentinoids

    • Quetiapine

    • Venlafaxine and Bupropion Abuse

    • Z-drug Dependence and Abuse

Misuse of Antipsychotics

  • Quetiapine as a Substance of Misuse:

    • Snorted at high dosages, producing sedative effects paired with reward levels (Chiappini and Schifano, 2018).

    • Noted as a trip terminator by psychonauts (Valeriani et al, 2015).

Mechanism of Benzodiazepines

  • GABA Cell Signaling:

    • Opening of chloride channels modulated by benzodiazepines enhances GABAergic signaling.

  • GABAA Receptor Mechanics:

    • Composed of five subunits around a chloride channel, which is probabilistically opened by GABA.

Benzodiazepine Dosage Equivalents

  • Table of Diazepam Equivalents:

    • Chlordiazepoxide: 25 mg

    • Clonazepam: 0.5 mg

    • Diazepam: 10 mg

    • Lorazepam: 1 mg

    • Lormetazepam: 1-2 mg

    • Nitrazepam: 10 mg

    • Oxazepam: 20 mg

    • Temazepam: 20 mg

Designer Benzodiazepines (DBD)

  • Definition of DBD:

    • Unapproved pharmaceutical drug candidates such as clonazolam, diclazepam, and others.

    • Structural modifications of registered drugs leading to potential abuse.

  • Regulations and Control:

    • Many DBDs have been placed under national control (ACMD, 2017).

    • Sold illegally as substitutes for known benzodiazepines.

Adverse Drug Reactions (ADRs) from Benzodiazepines

  • Cognitive Effects:

    • Memory deficits, attention deficits, increased reaction time, and impaired judgment.

  • Physical Effects:

    • Motor incoordination, dizziness, and sensory alterations.

  • Emotional Effects:

    • Depression, anxiety, emotional blunting, and suicidality.

Protracted Withdrawal Symptoms from Benzodiazepines

  • Common symptoms reported:

    • Emotional: anxiety, crying spells, and lack of emotions.

    • Neurological: seizures and balance problems.

    • Gastrointestinal: nausea and sleep disturbance.

Benzodiazepine Discontinuation and Mortality

  • Study Overview:

    • Comparative effectiveness regarding discontinuation effects on patients receiving stable benzodiazepine therapy.

    • Results indicating potential risks associated with discontinuation versus continuation.

Opioids: Seizures and Trends

  • Survey of novel opioids and illicit use discussions within the psychonaut community.

  • Findings included multiple synthetic opioids and their associative risks.

Analyzing Misuse of Dietary Pharmaceuticals

  • Binge Eating Disorder (BED) and misuse stimulants related to body image concerns.

    • Relationship between substance use and BED highlighted.

    • Misuse of GLP-1 analogues and potential anxiogenic effects detailed.

Conclusions

  • OTC misuse and non-medical use of prescription drugs are widespread; vulnerable populations primarily include adolescents and young adults.

  • Importance of education for clinicians and monitoring for misuse potential.

Future Steps in Research

  • Future studies required on the effects of NPS and systematized analyses of pro-drug communities for accurate toxicological understanding.