Novel Psychoactives

Cathinones

Introduction

Synthetic cathinones are drugs related to the naturally occurring Khat plant. They first appeared on the drug market for recreational used in the mid-2000s. They are taken for their stimulant and euphoric properties however their use has been associated with severe toxicity and death.

At least 81 synthetic cathinone derivatives have been described1. As a group they are often referred to as “bath salts”. Commonly used cathinones include:

  • Methadrone (M-CAT)  
  • Methcathinone  
  • Methylone
  • MDPV
  • Methylone
  • Alpha-Pyrrolidinovalerophenone (alpha-PVP)

Bupropion, a pharmaceutical used for depression and to aid smoking cessation, also belongs to the cathinone group.

They are mostly available as white or brown powders but are also available as crystals or less commonly capsules or tablets2

Toxicokinetics

Synthetic cathinones can be snorted, swallowed or injected. Onset following oral ingestion occurs between 15-45mins, whereas the effects occur within a few minutes of injection or snorting3. Duration of effect varies by dose and agent but is generally thought to be around 2-4 hours3

The exact mechanism of action is not fully understood and vary within the class, however cathinones are known to stimulate the release of dopamine whilst inhibiting the reuptake of adrenaline, noradrenaline and serotonin. 

Risk Assessment

Severity of toxicity will depend on the agent taken, the dose ingested and route of ingestion. The most common unwanted side effect is agitation, in some series reported in up to 66% of cases4.

Other commonly reported effects include:

  • Tachycardia
  • Hypertension            
  • Chest pain
  • Hyperthermic crisis
  • Hyponatraemia
  • Nausea and vomiting
  • Abdominal pain 
  • Seizures

Deaths have been reported mostly in relation to hyperthermic crisis and severe hyponatraemia.

Investigations 

  • Chem20
  • Serum Creatine Kinase
  • ECG

Management

Supportive Measures

Good supportive care is the mainstay of treatment.

Patient presenting with acute behavioural disturbance and sympathomimetic activation (evidenced by tachycardia and hypertension) should be managed along standard routes with sedation. Depending on degree of intoxication this may be in the form of oral benzodiazepine or parenteral droperidol (see module 1.6 Acute Behavioural Disturbance).

Manage seizure activity with titrated benzodiazepines

Hyponatraemia should be sought and corrected along standard lines. 

Hyperthermia should be treated promptly and those with severe hyperthermia (>40oC) should be intubated, paralysed and actively cooled. 

Disposition

Patients will mild to moderate toxicity can be managed under the toxicology team in the SSU with sedation as required. 

Those with more severe toxicity, particularly those with hyperthermia or severe hyponatraemia are likely to require ICU level care.

References

  1. European Monitoring Centre for Drugs and Drug Addiction. (2015). Perspective on Drugs: Injection of synthetic cathinones.
  2. Eurpean Monitoring Centre for Drugs and Drug Addiction. (2015). Synthetic cathinones drug profile.
  3. DrugWise. (2016). Mephedrone, methedrone, methadrone and methylone.
  4. Centers for Disease Control and Prevention (2011) Emergency department visits after use of a drug sold as “bath salts”– Michigan, November 13, 2010–March 31, 2011. MMWR Morb Mortal Wkly Rep 60(19):624–627

Synthetic Cannabinoid Receptor Agonists (SCRAs)

Introduction

SCRAs represent the largest group of NPS reported globally. With over 200 different compounds now available1.

They are typically sold as inert herbal products that have been sprayed with one or more SCRAs. They have strong effects on the endocannabinoid system.

They are often available in brightly colour packages with unusual names such as “Kronic” or “Spice”.

Examples of SCRAs available for purchase

There is little consistency, even within brands, as to the SCRAs present and often more than one SCRAs is present in a single package. 

Toxicokinetics

SCRAs are a large and chemically diverse group of molecules and therefore there is significant variation in their metabolism, potency, toxicity and duration of effects.

Potencies of up to 800x natural cannabinoids have been reported with some agents. 

Like natural cannabinoids they exert their desired effects by activation of CB1 and CB2 receptors. SCRAs have been shown to have much higher affinity for the CB1 receptor than natural cannabinoids, which explains their enhanced psycho-pharmacological activity2

Unlike natural cannabinoids, SCRAs do not contain cannabidiol (CBD), a chemical which moderates the effects of natural cannabis and is responsible for its anxiolytic, antipsychotic and anti-craving properties.

At higher doses, some SCRA compounds can act as MAO and 5-HT reuptake inhibitors, increasing the risk of serotonin toxicity. 

Onset of action when smoked is within minutes but can be delayed to 1-2 hours after ingestion. Duration of effect is variable with some compounds lasting 1-2 hours and others up to 8 hours3.

Risk Assessment

Evidence regarding the harms of SCRAs is still emerging. There are concerns that more recent formulations are more potent. 

Given the diverse and poorly studied group of chemicals sold as SCRAs the effects are equally varied. As well as the desired effects of relaxation, disinhibition and euphoria, various other effects have been documented.

Symptoms may include:

Neurological:

  • Psychosis
  • Acute behavioural disturbance
  • ALOC
  • Seizures
  • Confusion and short-term memory issues
  • Hypertonia
  • Myoclonus

Cardiovascular:

  • Tachycardia
  • Hyper/hypotension

Other:

  • AKI
  • Hyper/hypoglycaemia
  • Acidosis
  • Serotonin toxicity

Investigations

SCRAs do not produce a positive cannabinoid results on urinary drug screens (UDS).

Management

In general, most SCRAs users will not suffer adverse effects to the extent that will require hospital presentation. In those that do suffer severe effects there is no specific antidote and management is supportive. 

Supportive Measures

Patient presenting with acute behavioural disturbance and acute psychotic symptoms should be managed along standard routes with sedation. Depending on degree of intoxication this may be in the form of oral benzodiazepine or parenteral droperidol (see module 1.6 Acute Behavioural Disturbance).

Seizure activity is usually managed well with the use of titrated benzodiazepines.  

Disposition

Most patients are suitable for management by the toxicology team in the SSU until their intoxication has resolved. 

In case of severe toxicity including coma and organ disfunction admission to ICU will be required. 

Further reading

  1. Auwärter V, Dresen S, Weinmann W, Müller M, Pütz M, Ferreirós N. ‘Spice’ and other herbal blends: harmless incense or cannabinoid designer drugs? J Mass Spectrom. 2009 May;44(5):832–7. doi: 10.1002/jms.1558.
  2. Atwood BK, Huffman J, Straiker A, Mackie K. JWH018, a common constituent of ‘Spice’ herbal blends, is a potent and efficacious cannabinoid CB receptor agonist. Br J Pharmacol. 2010;160(3):585–93.
  3. Kleinschmidt K, Forrester MB. A comparison of ingested versus inhaled synthetic cannabinoids. Clin Toxicol. 2011;49(6):530–1.

Dimethoxyphenyl- N-[(2-methoxyphenyl)methyl ethanamine derivatives(NBOMes)

Introduction

NBOMes are a novel class of potent synthetic hallucinogens originally developed as 5-HT2receptor agonists for research purposes, but have recently become available for recreational use1.

Various forms are available but the most commonly reported in 25I-NBOMe. There have been a number of reported deaths associated with their use in North America, Europe and Australia.

They are often sold as a tablet, on blotting paper or as blue pills. They are colloquially referred to as “N-bombs” or “25I”, however they have also been sold, unbeknownst to users, as “LSD”, “synthetic LSD” or “acid”.

Toxicokinetics

NBOMes are generally taken sublingually or buccally, where they have an expected duration of action of 6-10hours, or by insufflation, where effects last 4-6 hours. 

Onset of action again depends on route of administration but can occur as early as 5 minutes and as late as 2 hours2.

Regardless of route used dosing is often variable and large doses have shown effects longer than 12 hours. 

Risk Assessment

Depending on the severity of toxicity presentations tend to fall into two categories.

The first is characterised by hallucinations and acute behavioural disturbance and the second involves more serious medical complications3,4.

Clinical features include:

  • Hallucinations
  • Acute behavioural disturbance
  • Hypertension
  • Tachycardia
  • Hyperthermia
  • Rhabdomyolysis +/- AKI
  • Seizures

Investigations

  • Serum creatine kinase level (looking for evidence of rhabdomyolysis)
  • Chem20 (looking for associated AKI)
  • ECG

Management

Supportive Measures

Patient presenting with acute behavioural disturbance and sympathomimetic activation (evidenced by tachycardia and hypertension) should be managed along standard routes with sedation. Depending on degree of intoxication this may be in the form of oral benzodiazepine or parenteral droperidol (see module 1.6 Acute Behavioural Disturbance).

Rhabdomyolysis, if present, should be treated with intravenous fluid hydration and monitoring of urine output (aiming for urine output 1-2ml/kg/hr). In severe cases with associated renal failure dialysis may be required.

Manage seizure activity with titrated benzodiazepines.  

Disposition

Most cases, without severe complications can be managed by the toxicology team in the SSU with sedation and IVF hydration. 

Patients are suitable for discharge when their ABD has settled, and investigations have shown no evidence of rhabdomyolysis or renal injury.

Patients with more severe toxicity particularly those with ongoing seizure activity and renal failure may need management in an ICU environment, particularly if dialysis is required. 

References

  1. Poklis JL, Charles J, Wolf CE, Poklis A. High-performance liquid chromatography tandem mass spectrometry method for the determination of 2CC-NBOMe and 25I-NBOMe in human serum. Biomed Chromatogr 2013; 27: 1794-1800.
  2. Erowid.
  3. Suzuki J, Dekker MA, Valenti ES, et al. Toxicities associated with NBOMe ingestion — a novel class of potent hallucinogens: a review of the literature. Psychosomatics 2015; 56: 129-39.
  4. Wood DM, Sedefov R, Cunningham A, Dargan PI. Prevalence of use and acute toxicity associated with the use of NBOMe drugs. Clin Toxicol (Phila) 2015; 53: 85-92