Özhan Yalçin on synthetic cannabinoids – the epidemic in Turkey

Psychiatric and cognitive effects of synthetic cannabinoids in adolescence

Özhan Yalçin 'Bonzai’ and ‘Jamaica’ may seem like exotic and attractive terms but in fact, they are associated with hundreds of deaths among adolescents in Turkey. Street names for synthetic cannabinoids, they were introduced into Turkey from Antalya in 2010, their usage gradually increased, with an epidemic declared between 2014 and 20161-6. Here, associate professor Özhan Yalçin (M.D), a child and adolescent psychiatrist in Istanbul, Turkey, highlights the dangers of these recreational drugs of abuse on adolescents, and how Turkey combated their use and attempted to treat the broad symptoms.

Adolescents were dying in streets and hospitals. Some were found comatose in parks and boulevards, and the disturbing images started to spread over the press and social media. Children as young as 9-10 years of age were found to be using these deadly and highly addictive synthetic cannabinoids. Parents became worried for their children, and with reason, as in some neighbourhoods, especially in Istanbul, adolescents using synthetic cannabinoids were outweighing the non-users.  

Prominent public health problem
During 2014 and 2016, synthetic cannabinoids usage in adolescents became the most prominent social, public health and security problem in Turkey. Cheap, and widely available on the streets, their use rapidly spread countrywide even being found in rural towns and villages. To date, more than 20 synthetic cannabinoid derivatives, all known by the terms ‘Bonzai’ and ‘Jamaica’, have been detected. These synthetic cannabinoids act on endogenous cannabinoid receptors in the body. All the derivatives varying in substance density, some being extremely strong and others also containing phencyclidine, ephedrine or opioid derivatives. Due to the number and diversity of these synthetic cannabinoids, the psychiatric and medical symptoms are wide-ranging.
 
Adolescents going undiagnosed
Synthetic cannabinoid use happened so rapidly in Turkey that paramedics and physicians had not experienced such cases and were baffled by its symptoms. One major issue was detecting the type of substance abuse using toxicological tests. Many of the derivatives were undetectable, combining this with the variety of symptoms these adolescents were displaying, many clinicians were left unable to diagnose the patient. Accident and emergency departments, as well as other medical centres, were inundated with intoxicated adolescents, unable to cope and correctly treat these individuals many were discharged too early, leading to unnecessary deaths, serious morbidity, and life-long disabilities. This provoked tension between the medical professionals in these departments and child and adolescent psychiatrists, who were later seeing these patients at psychiatric clinics presenting with severe medical conditions.
 
Manifestation of symptoms
Several users reported they had tried ‘Bonzai’ numerous times, but after one more 'hit' medical symptoms manifested with long-term costs. Their use has extensive and powerful side effects; from the initial symptoms of agitation, akathisia, sickness, vomiting, extreme sweating or chills, muscle pain, irritability, insomnia, appetite loss, and restless leg syndrome, to the more profound long-term consequences of violent behaviour, anxiety and panic disorders, homicidal behaviour, suicidal and self-injury behaviour, addiction, psychotic symptoms, manic behaviour, confusion, and death. Cases have reported respiratory or cardiac arrest leading to death, other cardiac problems (arrhythmias, myocardial infarction, or elevations in idiopathic creatine phosphokinase [CPK], troponin-I and highly sensitive C-reactive protein levels), hepatic complications (increased alanine [ALT] and aspartate aminotransferases [AST]), nephrological complications (usually leading to haemodialysis due to CPK levels >100,000 IU/L, electrolyte imbalance and anuria), rhabdomyolysis, delirium, confusion, epileptic seizures, cerebrovascular complications, movement disorders, hyperthermia, and neuroleptic malignant syndrome.

From the hundreds of synthetic cannabinoid cases that the country has seen, here Özhan Yalçin summarises evidence gathered of the psychiatric and cognitive symptoms and the treatment options that he and his colleagues have collected over this vulnerable time.

As mentioned, the symptoms vary. Patients may not display the same characteristics as the previous patient, mainly due to the multiple derivatives and the substance density of the compound.

Treatment options for psychiatric and cognitive symptoms
  • Agitation and violent behaviour: in our view, high potency antipsychotics (haloperidol) and other classical antipsychotics (chlorpromazine) should be avoided during periods of agitation. We have reported that these drugs can lead to neuroleptic malignant syndrome (NMS), rhabdomyolysis, hyperthermia, and severe CPK, ALT and AST elevations. Instead, benzodiazepines may be used for aggressive behaviour during the intoxication phase. In addition, quetiapine and low doses of risperidone could be used. Physical restraint has been shown to increase the risk of rhabdomyolysis, hyperthermia and NMS.
  • Anxiety and panic-like behaviour: benzodiazepines have been shown to be effective in these patients.
  • Homicidal, suicidal, or self-injury behaviour: clinicians could consider using quetiapine (Seroquel XR®) in these patients.
  • Severe cognitive decline, neuropsychological deterioration (even in mild use): these conditions mean that it is difficult to use cognitive-behavioural therapy, dialectical behavioural, and mindfulness techniques. Omega-3 and high doses of N-acetylcysteine may be useful to improve these conditions.
  • Addition, drug-withdrawal, and craving: synthetic cannabinoids are highly addictive. Consequently, drug-withdrawal is difficult and has similar symptoms with that seen in opioid withdrawal; agitation, akathisia, sickness, vomiting, anxiety, depression, extreme sweating or chills, muscle pain, fatigue, irritability, insomnia, appetite loss and restless leg syndrome. Some medications, such as N-acetylcysteine and gabapentin, which are useful in cannabis addiction, may be useful for relieving drug-withdrawal symptoms. Mirtazapine may be beneficial for alleviating sickness, vomiting, insomnia and depressive feelings. Quetiapine can help with insomnia and anxiety. In selected cases, shorter duration of benzodiazepines can be useful. Pregabalin and gabapentin have shown to decrease restless leg syndrome symptoms. We have also found topiramate and naltrexone are effective in relieving some of these symptoms.
  • Subthreshold psychotic and affective states: these are generally not seen during the intoxication phase and are resistant to antipsychotics. The use of high potency or classical antipsychotics, as mentioned above, can lead to more medical complications and should be avoided. These subthreshold psychotic states and paranoid ideations worsen the treatment alliance, motivation is decreased, and there is a high drop-out rate both in outpatient and inpatient clinics. We have found that quetiapine, risperidone and aripiprazole can be of use in these settings.
  • Development of psychotic symptoms and disorders: These can occur during the intoxication phase, but in some cases, symptoms have been seen long after this phase. Some of these patients may require hospitalisation in closed, high-safety child and adolescent psychiatric inpatient clinics. During intoxication, benzodiazepines may be useful in the early stages of the psychotic episode, later quetiapine, risperidone and aripiprazole may be safer. If there is a need for haloperidol treatment, it should be given intravenously.
  • Manic symptoms: We have experienced patients with extended manic features even after the use of synthetic cannabinoids. Benzodiazepines may be useful in the early stages of the manic episode, later quetiapine, risperidone and aripiprazole may be safer.
  • Delirium and confusion: This usually occurs during intoxication but in some cases can persist one to two weeks after initial drug use. These patients have a higher risk of death, thus medical investigations and early intervention are vital. Low doses of benzodiazepines, risperidone and quetiapine can be effective in these cases. Delirium is sometimes accompanied with psychotic episodes and agitation.
  • Synthetic cannabinoids on existing psychiatric conditions: Adolescents with a previous diagnosis of depression, anxiety disorder or attention deficit hyperactivity disorder (ADHD) who are already taking prescription drugs and then experiment with these synthetic cannabinoids can have profound effects. We have seen patients on atomoxetine or other psychostimulants for ADHD that have increased cardiological side effects if combined with synthetic cannabinoids. These drugs should be used with caution, and the risk-benefit ratio established.  
  • We have also found an increased risk of sexual abuse in adolescents who are taking these synthetic cannabinoids, and further side effects when combined with other psychiatric drugs.
“Synthetic cannabinoid use disorder”
This is a new era of cannabinoid use. From our experience, these synthetic cannabinoids are acting very differently to cannabis and other substances regarding their acute and chronic psychiatric-neuropsychiatric manifestations. Currently, there is very little scientific literature on this Turkish epidemic1-6. Thorough investigations are needed to understand further these synthetic cannabinoids, to determine any possible psychopharmacological agents for their treatment and any contraindications with other pharmacological agents. This information needs to be readily available and reliable. Eventually, with this information, we could see new editions of the DSM and ICD with a form of diagnosis for “synthetic cannabinoid use disorder” under the section on substance use disorders.
 
Light at the end of the tunnel
Since the first cases started to emerge, narcotic police and doctors have collaborated to identify the specific derivatives, as well as develop toxicological tests that are more sensitive and advanced. Blood and urine tests are now able to detect minimal traces that were once below the threshold limit.  

It was recognised that in order to combat synthetic cannabinoid use and treat these adolescents a multidisciplinary collaboration is needed between child and adolescent psychiatrists, paediatric cardiologists, paediatric neurologists, anaesthetists and intensive care units, as well as specialists in paediatric nephrology, paediatric gastroenterology, emergency medicine, and biochemistry and toxicology units.

Since 2016, synthetic cannabinoid use in Turkey has decreased. The narcotic police have set up successful inventions and operations, media coverage and educational programs in schools have raised awareness, and security teams by neighbourhood residents have prevented adolescents being able to obtain and use within neighbourhoods. It still remains a prominent public health and social concern, but we are in the right direction.

Raising awareness
Synthetic cannabinoids made their way into Turkey with devasting effects, they are cheap and do not require import as they can be produced illegally within a country. Therefore, the serious public health and social problems we have witnessed has already and will continue to radiate into other countries with equal effect.

With this article, we aim to raise awareness to the child and adolescent psychiatric community about these synthetic cannabinoids. By communicating our experiences, we will prevent further deaths of adolescents from these drugs in other countries.

 

References

1. Turkish Statistical Institute data: http://www.tuik.gov.tr/PreTablo.do?alt_id=1083. Accessed 19 June 2018.
2. Turkish Statistical Institute data. http://www.tuik.gov.tr/PreHaberBultenleri.do?id=27620. Accessed 19 June 2018.
3. Saribas S, Ulugol A. (2014) Struggle with bonzai: a review on synthetic cannabinoid abuse. Turkish Medical Student Journal 1 (2):86-93.
4. Uzbay T (2015) Ulkemizdeki temel sorunlar ve madde bagimliligi ile mucadele. In: Uzbay T (ed) Madde bagimliligi. Tum boyutlar?yla bagimlilik ve bagimlilik yapan maddeler. Istanbul Tip Kitabevi, Istanbul, 2015, pp 367-378.
5. Demirci AC, Erdogan A, Yalcin O, Yildizhan E, Koyuncu Z, Eseroglu T, Onder A, Cüneyt E (2015) Sociodemographic characteristics and drug abuse patterns of adolescents admitted for substance use disorder treatment in Istanbul.  Am J Drug Alcohol Abuse 41 (3):212-219.
6. Mutlu C, Yalcin O, Demirci AC, Bozbey S, Yuksel ME, Erdogan A (2014) Characteristics of heroin users admitted to child and adolescent substance abuse treatment and support center of Turkey. Turkish Association for Psychopharmacology, 6th International Congress on Psychopharmacology, 2nd International Symposium on Child and Adolescent Psychopharmacology, Klinik Psikofarmakol Bülteni 24 (Suppl 1): 317.