Ecstasy

Author: John-Paul Loughrey / Editor: Elizabeth Herrieven / Reviewer: Emma Faragher / Codes: A4 / Published: 01/09/2014 / Reviewed: 09/07/2024

(Thanks for Dr Fraser Denny for the use of his slides What is in a Green Rolex?, and to Dr Richard Stevenson for his algorithm published freely online.)

1. What is ecstasy?

• MDMA (3,4-methylenedioxy-N-methylamphetamine) is an empathogenic drug of the amphetamine and phenethylamine classes of illicit drugs, commonly referred to as Ecstasy. Other colloquialisms for Ecstasy – E, X, XTC, Mandy (pure MDMA), Superman, Rolexes, Mitsubishis, Crystal, Eckies.

• Originally developed by Merck in 1912, used in 1953 by the US Army in psychological warfare tests and in the 1960s as a psychotropic drug to induce disinhibition (marriage counselling!). Emerged as a party drug in the 1970s and 1980s.

• Causes release of Serotonin in the brain (and some dopamine). Central and peripheral catecholamine release also occurs.

• Metabolised predominantly in the liver (CYP450), half-life 6-10 hours, recreational effect 3-5 hours, renally excreted.

• Onset of effect around 30 minutes from ingestion – peak effects at 60-90 minutes.

• Significant cracked-out symptoms for up to 2 days later (due to significant depletion of serotonin) – depression can be a common symptom of ecstasy abuse.

• Rarely pure MDMA in ecstasy – multiple adulterants including PCP, Ketamine, PMA (essentially a really, really toxic serotonergic drug of the amphetamine class, known as Dr. Death – see further reading), Mephedrone.

• Pure MDMA is a white, crystalline powder. It is usually stamped into tablets of varying colours and logos (extremely useful to ask about the colour and imprint on the tablet for public health surveillance and Police investigation when dealing with patients with ecstasy ingestion) but is sold as a white powder. Both powder and pills are usually taken orally, occasionally smoked or snorted, and rarely injected.

• Pills usually contain 30-150mg MDMA (higher quantities potentially dangerous, especially if paediatric patient or multiple doses ingested).

• Class A drug in the UK – illegal to possess, give away or sell. Possession can be punished with 7 years in jail, supplying can result in lifetime jail sentence and an unlimited fine.

2. What is the scope of the problem in the UK?

• The office of national statistics puts ecstasy use in the year ending March 2023 at 1.1% of 16 to 59 year olds, down from 1.4% in 2020. In the 16 24 year old age group use of ecstasy was 2.4%, again down from 2020.¹
• Strength and cost of pills vary significantly through Europe and exact data isnt easily available; meaning that people will often not know exactly what they are buying. We do have data that suggests the strength of both pill and powder forms of ecstacy have increased significantly over the last 20 years. Pills range from 3mg to 400mg.³

• There are also issues with both pills and powder being aldulterated with other substances which change the duration or intensity of effect. This includes several cathinones which can cause prolonged stimulation and an urge to re-dose quickly.⁴

• Its difficult to get exact figures for deaths due to ecstacy as many involve more than one substance misuse and over 20% of deaths due to substance misuse in 2022 did not mention the exact substance on the death certificate.²
• In general death due to drug misuse is highest in 40 to 49 year olds and is higher in the north than the south of the UK.²

3. How do these patients present?

• Severe toxic features are usually idiosyncratic (no correlation with dose ingested or previous duration of exposure). Serious toxicity or death is usually associated with blood concentrations of 0.5 – 10mg/L with the lowest reported as 0.11mg/L
• Serotonergic crisis can be subdivided by the severity of symptoms   courtesy of Dr Richard Stevenson:
• Mild Toxicity
  • Anxiety
  • Restlessness
  • Palpitations
• Moderate Toxicity
  • Pyrexia (38-39.9)
  • Tachycardia
  • Sweating
  • Clonus & Hyperreflexia
  • Agitation
  • Hallucinations
• Severe Toxicity
  • Severe pyrexia > 40
  • Tachycardia & Hypertension (may be labile)
  • Sweating
  • Hypertonicity / Rigidity & Hyperreflexia
  • Obtunded GCS
  • Rhabdomyolysis
  • Hypoglycaemia

Mnemonic for the Hunter criteria for Serotonin Syndrome (some of them are a bit iffy!)

S – Spontaneous clonus (+ inducible clonus)

H – Hypertonicity, hypertension, hyperthermia

O – Ocular clonus

T – Tremor, tendon reflexes increased

S – Sweating & Struggling (agitated)

– Hunter criteria

4. Initial Assessment and Investigations

A to E and check TOXBASE (theres an app for TOXBASE, which is often much faster than using a Trust computer and looking for the password).

In the very unwell call for help early and get the patient assessed in the appropriate place, such as resus.

A – Keep airway clear and consider the need for intubation if falling or low GCS

B Monitor SATs and RR, use O2 as needed and consider CXR if concerns about aspiration and the patient is stable enough to do so.

C ECG in all symptomatic patients and repeat this if further concerns such as an initially abnormal trace or new symptoms. IV access and bloods: FBC, U&E, LFT, CK and INR if there are features of toxicity. Fluid resuscitation if hypotensive. Echo may be needed in severe cases to assess the benefit of vasopressors  and inotropes.

D Keep an eye on GCS which can change, check blood sugars and treat appropriately. Ensure you check pupil size and ankle clonus as well. Single self terminating brief seizures dont need treatment however prolonged or repeated seizures do. Always check toxbase for treatment in these cases. Barbiturates are recommended second line after benzodiazepines to avoid phenytoin. Check BM (blood glucose can be very low and resistant to correction), U&E, Ca, Mg, Phosphate and a blood gas if seizures occur.

E Temperature, treat hyperthermia as a priority. Remember to fully examine the patient to ensure no co-existing issues such as trauma especially if they are unconscious and cant give a history.

Others:

• Urine dip (blood and myoglobin)
• Quantitative MDMA levels rarely helpful many are toxic from contaminants, some patients have spectacular idiosyncratic reactions to low doses
• Urine tox screen useful for confirmation and detection of contaminants
• Police and Toxicology / NPIS useful for discussing testing of remaining pills to establish exact contents
• Pregnancy test in women of childbearing age (I would suggest doing this in all overdose / toxicity patients)

5. Prognostic Indicators

Flow diagram based on the Hunter Serotonin Toxicity Criteria

Poor prognostic features include

• Persisting obtunded conscious level
• Hypoglycaemia resistant to corrective measures
• Rhabdomyolysis and resistant hyperkalaemia
• Fever correlates with severity and mortality (Temp >40 – severe toxicity)6. management plan

6. Management Plan

• TOXBASE has a clear step-by-step management plan that outlines a pragmatic and safe approach
• Remember, the contaminants may not behave as MDMA toxicity hyperthermia can be resistant to treatment. Check TOXBASE thoroughly and discuss with the clever and interesting folks at NPIS they are super friendly and have helped me with many a difficult case!
• Dr Richard Stevensons algorithm was devised in Scotland amidst an outbreak of Ecstasy related deaths see below.

7. Appropriate Disposition

• Patients should be monitored for at least 4 hours (8 hours with modified release preparations)
• Patients with mild symptoms should be managed as above and admitted to a monitored bed for regular observation (cardiac monitoring, BP, temp, BM).
• Any moderate symptoms – start treatment and consult EM senior – need a watchful eye (consider moving to Resus), early intervention and consideration for escalation to a high level of care (eg HDU)
• Patients with severe symptoms (rhabdomyolysis, hyperthermia, hypoglycaemia, hyponatraemia, reduced LOC) should be considered for ICU referral and admission – consult EM senior (Registrar or Consultant) early and get help.

References

1. Drug misuse in England and Wales: year ending March 2023. Census 2021. Office for National Statistics.
2. Deaths related to drug poisoning in England and Wales: 2022 registrations. Census 2021. Office for National Statistics.
3. Statistical Bulletin 2023 price, purity and potency. European Union Drugs Agency (EUDA)
4. 2022 update on MDMA. Drugs and Alcohol Information and Support.

Further Reading and Resources

• Center for Substance Abuse Research, USA.
• Hall AP, Henry JA. Acute toxic effects of Ecstasy (MDMA) and related compounds: overview of pathophysiology and clinical management, BJA: British Journal of Anaesthesia, Volume 96, Issue 6, June 2006, Pages 678685.
• Hahn I. MDMA Toxicity. Medscape, updated: 2023.
• Ben-Abraham R, Szold O, et al. ‘Ecstasy’ intoxication: life-threatening manifestations and resuscitative measures in the intensive care setting. Eur J Emerg Med. 2003 Dec;10(4):309-13.
• Gahlinger PM. Club drugs: MDMA, gamma-hydroxybutyrate (GHB), Rohypnol, and ketamine. Am Fam Physician. 2004 Jun 1;69(11):2619-26.
• Kalant H. The pharmacology and toxicology of “ecstasy” (MDMA) and related drugs. CMAJ. 2001 Oct 2;165(7):917-28.

PMA

• para-Methoxyamphetamine. Wikipedia
• PMA – the ecstasy and the agony. The Guardian, 2013.
• Seven deaths are linked to fake ecstasy tablets, police say. BBC News, 2013.

Treatment of Serotonin Toxicity

• Treatment of Serotonin Toxicity NHS Greater Glasgow and Clyde, 2007- Dr. Richard Stevensons poster – freely available, excellent resource and quick reference.
• Toxbase (theres also a useful App and telephone numbers for local NPIS)

Ecstasy in the Media

Film: Irvine Welshs Ecstasy

Songs: XTC by Boys Noize, Ebeneezer Goode by The Shamen, Sorted for Es and Whizz by Pulp, La La Land by Green Velvet, One Night in New York City by The Horrorist, Tainted Love by Soft Cell, All Gold Everything by Trinidad James, Take Ecstasy With Me by The Magnetic Fields, Molly by Tyga, Mercy by Kanye West, The Asphalt World by Suede.