East Asian Arch Psychiatry 2012;22:31-3

CASE REPORT

香港新兴滥药形式 —— 合成大麻素引致的急性精神障碍

CK Tung, TP Chiang, M Lam

董梓光、蒋天宝、林明

Dr Chi-Kwong Tung, MRCPsych, Tuen Mun Substance Abuse Clinic, Castle Peak Hospital, Hong Kong SAR, China.
Dr Tin-Po Chiang, MRCPsych, FHKAM (Psychiatry), FHKCPsych, Tuen Mun Substance Abuse Clinic, Castle Peak Hospital, Hong Kong SAR, China.
Dr Ming Lam, MRCPsych, FHKAM (Psychiatry), FHKCPsych, Tuen Mun Substance Abuse Clinic, Castle Peak Hospital, Hong Kong SAR, China.

Address for correspondence: Dr Chi-Kwong Tung, Tuen Mun Substance Abuse Clinic, Castle Peak Hospital, Hong Kong SAR, China.
Tel: (852) 2456 7214; Fax: (852) 2463 1644; Email: ricky.cktung@gmail.com

Submitted: 14 September 2011; Accepted: 4 November 2011

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Introduction

Reports of synthetic cannabinoid abuse in the form of a ‘herbal smoking blend’ or incense (often with the statement ‘not for human consumption’) began to emerge in the early to mid-2000s. Best known by the brand names ‘Spice’ and ‘K2’, it gained popularity among young substance abusers in Europe and later North America for its relatively low costs compared to cannabis, easy availability by online purchase, and being less noticeable to parents, school and authorities.¹ Despite a rapid rise in its abuse, there is limited scientific evidence regarding its psychopharmacological effects on humans. In Hong Kong, its misuse was largely unheard of before 2010. We present the case of a young local Chinese man who developed acute mental disturbance caused by K2 abuse.

Case Report

We report on a 36-year-old male real estate agent who had good physical health and known history of abuse of multiple psychoactive substances. He also indulged in a period of heroin abuse by intravenous injection when he was a teenager. In the past 10 years, he was abusing codeine- containing cough syrup and cannabis on a daily basis, and he had established dependence syndrome on them. There was no sustained cessation of substance abuse in the past, except for brief periods of abstinence achieved in prison and hospital settings. He reported no history of regular alcohol consumption. An aunt and a grand-uncle were said to have mental illness (without history of substance abuse) for which they received lifelong treatment, but further details were unavailable as both had died long time ago. His brother suffered from unipolar depression without a history of substance abuse.

In late 2009, he presented to a psychiatric hospital with an episode of acute psychotic disorder, characterised by florid persecutory delusion and auditory hallucination. He was diagnosed as having schizophrenia-like psychotic disorder due to abuse of cough syrup, as urine toxicology screening yielded ephedrine / pseudoephedrine and promethazine, which were common constituents of cough syrup. He was prescribed with low-dose antipsychotics (perphenazine 4 mg / day) and resolution of symptoms was observed in a matter of days. He continued illicit drug abuse soon after his discharge from hospital. He reported using 5 joints of cannabis and about 40 mL of codeine-containing cough syrup per day; however, he had not relapsed into another psychotic episode. He could get on with his job, and was not observed to have any mental abnormality during his follow-up sessions in substance abuse clinic. Therefore, perphenazine was eventually stopped upon his request in mid-2010. Six weeks later, he became irritable, and started swearing at his wife, children and clients over trivial matters. He was observed by family members to be restless and pacing around at home. He slept poorly at night. His thoughts and behaviour also became disorganised, exemplified by irrelevant speech, sending chaotic text messages to his wife’s mobile, and practising Kung-fu in public. The acute mental disturbance persisted for 2 weeks before he was brought to the hospital by his family.

He was agitated when brought to emergency department; he was physically restrained and injected with intramuscular midazolam for rapid tranquilisation. On the next day he was transferred to psychiatric ward; mental state examination on admission found him to be very restless and easily annoyed. He demonstrated brief, fast-paced speech with no clear formal thought disorder. No other manic or psychotic symptom was elicited. He showed poor insight into his mental disturbance and denied the disorganised behaviour reported by his family. Physical examination revealed a blood pressure of 150 / 90 mm Hg, heart rate of 95 beats/ min, and profuse sweating. On-the-spot urine toxicology screening by class-specific immunoassay was negative for opioids and cannabinoids, while laboratory-based high- performance liquid chromatography detected ephedrine / pseudoephedrine, promethazine and dextromethorphan.

His elevated blood pressure and perspiration completely resolved after 1 day, as did his restlessness and irritability by 3 days after his admission. The remission was spontaneous without use of any sedatives or antipsychotics. No specific withdrawal syndrome was observed.

After his mental state stabilised, he reported that 4 weeks prior to onset of his mental disturbance, he began using a synthetic cannabinoid sold under the brand name K2 as a substitute of cannabis. It was bought from the same drug dealer who sold him cannabis. He described K2 as a dried vegetative preparation, which could be rolled into a cigarette and smoked. It costed him HK$600 for 1/8 ounce (about 3.54 g), which could be rolled into about 20 joints. He was using 3 joints (about 0.53 g) per day until his admission to hospital (consumption was reported to remain similar even after onset of the mental disturbance). He reported that a relatively small amount of K2 produced much more intense euphoria than cannabis. On the other hand, he had stopped using codeine-containing cough syrup since using K2 regularly. However, he continued using another non–codeine containing cough syrup preparation (40 mL per day), which he claimed was for sole purpose as a cough remedy. That preparation contained promethazine, dextromethorphan and ephedrine, which was compatible with his urine toxicology screening results. His physical and psychiatric condition was observed to be stable for another 10 days in the ward, whereupon he was discharged from hospital. He continued to regularly attend follow- up sessions at the substance abuse clinic over the next 9 months. He denied any relapse into substance abuse, which was consistent with the negative results of urine toxicology screening. He displayed no further mental abnormality and resumed his job without any difficulty.

Discussion

In the present case, a functional acute psychotic disorder as an alternative explanation for this presentation was theoretically possible. Its very brief duration, lack of associated acute stress, absence of typical schizophrenic symptoms, and spontaneous resolution without pharmacological treatment, however, argue against this possibility. On the other hand, the possibility of another episode of psychosis induced by cough syrup abuse cannot be entirely ruled out, given his continued abuse of cough syrup and relevant history. It is worth noting, however, that the current episode of acute mental disturbance was predominantly one of psychomotor agitation, which differed from his previous episode that was characterised by florid delusions and hallucinations. His recent cough syrup abuse was also reported to be relatively stable and at a low level of consumption. Therefore, the introduction of synthetic cannabinoid abuse and its direct psychotropic effect remains the most probable explanation for his acute mental disturbance. Regrettably, no body fluid was stored when he was admitted to the hospital, therefore toxicology testing for this particular synthetic cannabinoid could not be performed. Thus, definitive evidence of actual consumption of this synthetic cannabinoid is lacking.

When these ‘designer drugs’ first went on sale, it was thought that they achieved cannabis-like effect through a mixture of legal medicinal herbs. In 2008, laboratory analysis in Germany showed that many of the characteristic ‘fingerprint’ molecules expected to be present from its claimed herbal ingredients were actually absent, suggesting that its ingredients might not be the same as those listed on the package.² In January 2009, researchers in Germany announced that synthetic cannabinoid CP47-497 was identified as an active ingredient in Spice.³ Subsequently, other potent synthetic cannabinoids like JWH-018, JWH- 073, and HU-210 were found in other samples of Spice.⁴

Presumably, a solution of these cannabinoids had been sprayed onto the herbal mixture as vehicles for delivery. Intra- and inter-batch variability of composition of synthetic cannabinoids is considerable, thus there is a higher potential for overdose than with cannabis. These synthetic cannabinoids mimic the effects of tetrahydrocannabinol (THC) by interacting with the cannabinoid receptor type 1 in the brain,⁵ and binding much more avidly to this receptor than THC (as measured by the affinity constant Ki).⁶ Thus, it is very likely that the cannabis-like effects of Spice are due to the presence of these synthetic additives. So far, there is limited literature available on detailed pharmacology, toxicology, and effect on physical and psychological health of these synthetic cannabinoids. However, there is a growing body of information about their adverse psychiatric effects from case reports. One report described Spice use as a trigger for an acute exacerbation of psychosis in a man with a history of recurrent cannabis-induced psychotic episodes and a family history of psychosis.⁷

Another report from Germany detailed an individual fulfilling diagnostic criteria of dependence syndrome after 8 months of regular Spice abuse, who developed withdrawal phenomena after abstinence.⁸ There was a self-experiment on the effects of Spice use, in which conjunctival injection, tachycardia, xerostomia, alteration in mood and perception were described.⁹ Anxiety was reported to be a prominent presentation in 2 young women who presented to an emergency department for Spice intoxication.¹⁰ Anxiety and psychotic symptoms were commonly reported after use of ‘Aroma’, a JWH-018–containing product, in a group of 15 patients in a forensic psychiatry setting, whose psychiatric illness was previously stable.¹¹

Being a ‘legal’ alternative to smoking cannabis was a major appeal to Spice users, as the manufacture, sale, or possession of these smoking blend products were legal in most countries of the world before 2008. Following discovery of JWH-018 and CP-47-497 in a sample of Spice, the German government swiftly made all products containing these substances subject to the Narcotics Law from January 2009 onwards,¹² and other European countries and several states in the United States soon followed suit. Reports of K2 abuse in Hong Kong began to appear in local newspapers in early 2010; in the same year, K2 was first confiscated by Hong Kong SAR police. The government was aware of the danger of its growing popularity among young substance abusers, and an amendment was made to the Dangerous Drugs Ordinance in April 2011,¹³ subjecting synthetic cannabinoids to the same control as for other dangerous drugs.

However, legislation alone may not be enough to halt the widespread use of these drugs. Following classification of Spice as a Class B controlled drug by the United Kingdom in December 2009, these classified synthetic cannabinoids continued to be present in Spice purchased from websites on the internet.¹⁴ Furthermore, new synthetic cannabinoids not covered by the legislation started to appear in these products, probably as a means of circumventing the law.¹⁵ Enforcing the law for these synthetic cannabinoids is difficult, because they do not test positive for cannabis or other illegal drugs in conventional urine toxicology screening procedures (possibly with the exception of HU-210, which resembles THC in its chemical structure). Methods for rapid screening for JWH-018¹⁶ and CP-47-497¹⁷ by mass spectrometry in human urine have been successfully developed, but are not yet widely available.

Conclusion

Given its novelty status, lack of knowledge of its danger, and escape from detection by conventional urine toxicology screening, it is possible that popularity of K2, Spice and other smoking blend products containing synthetic cannabinoids will continue to grow in Hong Kong. Currently there is limited clinical evidence to guide management of adverse sequelae after their use. Further educational efforts are needed to inform the public about its threat. Meanwhile, clinicians should have heightened vigilance and consider the possibility of synthetic cannabinoid abuse in patients with a history of drug abuse, who present with unexplained mental disturbance and negative urine toxicology.

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