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.  

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.

• 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.

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.

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