Prescription drug found in synthetic cannabis product

The Ministry of Health announced last week that a particular variety of the ‘synthetic cannabis’ smoking blends, Kronic – Pineapple Express, is being recalled due to the presence of a prescription drug.

Herbal smoking blends treated with legal, psychoactive synthetic cannabinoids have been causing public debate over their effects and accessibility.

Testing conducted by ESR revealed that the Pineapple Express variety of the popular legal smoking blend Kronic also contained the controlled benzodiazepine drug, phenazepam.

You can read the Ministry of Health press release here.

Update: On Saturday (2nd July) another brand of synthetic cannabis, Juicy Puff Super Strength, was also recalled following detection of phenazepam in samples tested by ESR.

The Science Media Centre contacted experts for more information on the detection of phenazepam in synthetic cannabinoid smoking blends. We will update our site with further comments as they become available.

Feel free to use these quotes in your stories. To follow up with these or other local experts, please contact the Science Media Centre.

UPDATED:

Dr Paul Quigley, Emergency Medicine Specialist, Wellington Hospital:

Has this specific brand (Pineapple Express) been associated negative symptoms in users that could be attributed to phenazepam?

“Our experience with any of the available non-nicotine combustible recreational drugs is very limited.  There have been small numbers of presentations over the last 2 years, with initial patients presenting after taking Dream or Spice brands. We could not say that anyone brand has presented more often than another.

“Our most common patient presentations are mainly because of symptoms of anxiety and agitation.  These may be associated with short self-limiting episodes of hallucination.  All presentations have been of the mild variety and have needed short-term observation and reassurance.  These symptoms would not consistent with benzodiazepine use, but is consistent with cannabinoid effect.

“Around the country there have been reports of patients presenting with sedation and also dysphoria which would be more consistent.

What are the possible risks associated with smoking a drug like phenazepam? (as opposed to oral ingestion)

“Smoking any drug increases its potency and has a pharmacological effect similar to injecting the drug.  This means the effects of the drug are more immediate and also stronger than taking the same drug orally.  This has been shown to markedly increase the potential for addiction because the stimulation of the reward system of the brain is more immediate and with a stronger response.  With a drug like phenazepam this would be of particular concern as all benzodiazepine drugs have the potential to cause addiction.

“We have very limited knowledge or experience of Phenazepam in New Zealand. However, Benzodiazepines all have the same clinical action, side effects and toxicology.  Benzodiazepines are clinically used to stop epileptic seizures, induce sedation and reduce anxiety.  They can be used to reduce the symptoms from drug and alcohol withdrawal.  They are prescription only medications and in the past some have been removed from the pharmaceutical market such as flunitrazepam because the potential for harm was greater than the benefit.

“Ironically, benzodiazepines are addictive and cause a very dangerous withdrawal syndrome with anxiety, paranoia and epileptic seizures.  This may be what some Emergency Departments are experiencing in patients presenting days after smoking these agents.  It could be a form of withdrawal.

“Benzodiazepines have other side effects that are of concern when being used as a recreational drug.  They cause both retro-grade (things in the past) and ante-grade (future events) amnesia.  It is this effect that makes benzodiazepines a drug commonly used in drug-facilitated sexual assault.  The victim cannot recall whether the events really happened or not, making history taking very difficult. It is concerning that people are smoking a benzodiazepine that can cause amnesia, they potentially not be able remember what they were doing or what they were going to do.  They would be extremely vulnerable.”

Are there known interactions between cannabinoids and phenazepam?

“The principal effect of Benzodiazepines is to cause sedation and reduce anxiety.  This effect would be additive to any other substance that causes sedation.  Of greatest importance would be the interaction between Alcohol and benzodiazepines.  This causes potent sedation and loss of motor control, this can be to the level of coma.  People have died from taking combinations of alcohol and benzodiazepines, this has been because of respiratory depression.  As many recreational drug users also consume alcohol there is significant potential for excessive sedation to occur.

“There would be a similar increase in sedative effect to those of the cannabinoids but this would be very variable.  Some cannabinoids actually cause anxiety and agitation; in this situation benzodiazepines would actually suppress symptoms and reduce anxiety.  Many recreational drug users choose Benzodiazepines to enable sleep after taking stimulant drugs such as methamphetamines.”

“In Summary: Smoking a benzodiazepine like Phenazepam has the potential to be very dangerous.  The smoker would be at risk of;

  • Increased and unexpected sedation
  • Loss of current and future memory
  • Risk of addiction and dependency on benzodiazepines
    • This could cause a withdrawal / craving syndrome on cessation of smoking.

“Users smoking phenazepam-laced products would potentially be at risk of harm from others while intoxicated.

“They would also be significantly unsafe to drive.”

Dr Leo Schep, Toxicologist, National Poisons Centre

“We know very little on the toxicology of these analogues [synthetic cannabinoids] in humans. Presently it is based on phone inquiries to the National Poisons Centre (NPC), cases in Dunedin hospital ED and the few papers describing presenting clinical signs and symptoms at hospitals. These include tachycardia, vomiting, drowsiness, disassociation/hallucinations, tight chest, psychosis and chest palpitations.

“The only predominant clinical effect that could be attributed to phenazepam is drowsiness, though this has also been reported overseas, where there is no evidence of this contaminant.

“Phenazepam is a benzodiazepine and like all benzos, there is a cumulative central nervous system depression (drowsiness, stumbling, coma and in extreme cases a risk of respiratory depression) when taken with alcohol. We have no idea of their interaction with the analogues but it may potentially influence their activity, possibly further contributing to CNS depression.”

Dr Keith Bedford, General Manager of forensic research at Environmental Science and Research (ESR):

“ESR has been monitoring the situation with these so-called “legal highs” since 2009, when Spice was the first such product that came to widespread notice. Since that time, we have been asked to test various products or material by Customs, the Ministry of Health and police.

“This finding was not expected. We were simply screening the product when this unexpected peak jumped out at us. It turned out to be phenazepam.

“Under the Medicines Act, there is a provision that excludes incidental low-level contamination, which is defined as 10 ppm (parts per million) of the material, which is why that’s referred to in the information that came out today. I’m confident that the levels [of phenazepam] found in Kronic Pineapple Express are well above that threshold.

“They’re consistent with a low therapeutic dose of this drug when it’s taken conventionally by injection or mouth. Of course, when it’s smoked, that’s a different ball-game. There’s not a lot know about the effects of this substance when smoked.

“Another concern I have is that we don’t really know the techniques that are used to prepare this material, or what quality control might be involved. Therefore, we don’t know whether there might be variable concentrations in different packets of this product, or variation within a packet.

“My suspicion is that phenazepam is contributing to the effects of the product, including reports of adverse effects. I think that has clouded the public debate on these synthetic cannabinoids, because in my opinion it is quite probable that at least part of the adverse effects have been due to this adulterated Pineapple Express product, which seems to be one of the more common products in the market.

“As well as phenazepam, we have found the synthetic cannabinoids JWH-018 and JWH -073 — these are two of the most common synthetic cannabinoids around. There’s also another one which is less common — RCS-04, and it’s butyl analogue which doesn’t even have it’s own number. You’ve got cocktail of these four substances plus phenazepam in Pineapple Express.

“What the combined effect of that cocktail would be is unknown, let alone in combination with other substances that might be consumed, such as alcohol. There’s a potential for quite unexpected kinds of adverse reactions.

“In the literature, I’ve seen suggestion that there are a significant number of these synthetic cannabinoid-type substances in circulation. One report named 35, another suggested there might be 80 or more. We’ve seen about a dozen of them in New Zealand in one product or another.

“In terms of toxicology and pharmacology, I think there’s an appalling lack of information available on these substances.

“I strongly support classifying these as restricted substances, which puts a significant amount of regulation and control around them, without banning them.

“At the moment, our legislation is based on actions being taken on evidence of harm. I am strongly supportive of the Law Commission review of the framework for regulating drugs and medicines, which recommended putting the onus of proof onto the distributor or supplier to undertake some form of safety or toxicity testing.”

Dr Paul Gee, Emergency Medicine Specialist at Christchurch Hospital:

“Phenazepam is a sedative  anticonvulsant.  It belongs to the benzodiazepine class which includes valium and clonazepam.  It was developed in the Soviet Union in 1975 but is not widely used as a medicine.  Phenazepam has been used in the treatment of neurological disorders such as epilepsy, drug withdrawal and anxiety disorders.  It is very potent and long acting.

“It has become a drug of abuse as it is not controlled in many countries.

“Its extreme potency makes titrating effect difficult and overdose is therefore more likely.  Recreational use in combination with other drugs has resulted in deaths.  The most common routes of use are ingestion and injection. Only basic chemical data is available and it does not appear to be heat stable.  Applying heat will cause pyrolysis releasing chlorine and bromine.”