Abstract
Popularity of synthetic cannabinoids among US military service members has risen over the last several years, leading to an increase in hospitalizations and legal actions stemming from its use and possession. Although synthetic cannabinoids, collectively referred to as “Spice,” are similar in structure to the active metabolites found in cannabis, significant concerns exist regarding the severity of short- and long-term medical and psychiatric sequelae. This article presents a case, in which a patient experienced severe medical and psychiatric symptoms far exceeding the severity and duration typically resulting from cannabis use.
Introduction
Introduced into US and European markets in mid-2000, use of synthetic cannabinoids has risen in popularity, particularly in special populations such as military service members. Its popularity with military service members can be generally attributed to its quality as structurally distinct from existing banned compounds, thereby presenting challenges in development of appropriate legal policy as well as challenges in detection of its metabolites. Being a new phenomenon of the last decade, existing medical literature is sparse in its coverage of synthetic cannabinoids, generally presuming its effects to be akin to cannabis. This assumption, however, may be misguided as poison control centers have seen substantial increase in calls due to synthetic cannabinoids. This paper presents such a case, in which a patient with synthetic cannabis dependence developed unusually severe and persistent medical and psychiatric symptoms.
Case
A 20-year-old Hispanic male soldier who had recently returned from deployment in Iraq was brought to the emergency department (ED) because of a change in mental status. Three days prior, the patient had completed a 20-day confinement to barracks for synthetic cannabinoid use. Upon arrival of Emergency Medical Services, the patient was awake but uncommunicative and unable to follow commands. In the ED, the patient was noncompliant and combative and physical restraints were applied; 2 mg/mL of lorazepam were administered. In the ED, the patient would suddenly awake and become increasingly agitated, rapidly reaching a level of agitation at which, even in restraints, he posed a risk to staff and to himself.
Patient History
The patient was the oldest of 3 siblings from an intact union. He described his childhood as “happy.” Academically he was average and graduated high school on time. The patient began consuming alcohol at the age of 15; drinking daily during high school. He tried marijuana 3 times prior to joining the US Army, but denied regular use as well as the use of any other drug prior to joining the military.
Upon completing basic training he was stationed to Fort Bragg, North Carolina, and befriending several soldiers who routinely used spice. He subsequently deployed to Iraq for 12 months, and after his return from Iraq the patient tried “plant feeders.” Plant feeders (mephedrone) are a type of synthetic stimulant and entactogen drug of the amphetamine and cathinone classes. The use of these “plant feeders” was infrequent. However spice continued to be consumed daily in conjunction with marijuana when available.
Hospital Course
The patient was admitted to the hospital following stabilization in the ED. He was unresponsive to questions, though he appeared alert. All laboratory and radiological reports were reviewed and found unremarkable.
Given the patient's concerning behavioral presentation, a psychiatric interview concluded that he was experiencing a disturbance in consciousness, change in cognition, and attention impairment consistent with delirium.
On the second day of hospitalization, the patient was awakened at various times and found to be initially responsive. He would, however, break eye contact, fixing his vision on peripheral objects such as the television. At approximately 10:45, the patient became tachycardic with a heart rate of 160 beats per minute (bpm) displaying psychomotor agitation. The patient was given 2 mg of lorazepam and his heart rate returned to normal and his psychomotor agitation was resolved.
Around noon on day 3 of hospitalization, the patient attempted to remove his intravenous (IV) line resulting in restraint. He was administered 2 mg lorazepam. The patient continued to be combative, pulling out the IV catheter from his arm. Ten minutes later, an additional 1 mg lorazepam; followed 10 minutes later with 25 mg of diphenhydramine and 5 mg halperidol. After approximately 15 minutes, the patient became drowsy and his heart rate returned to normal.
On the fourth hospital day, the patient became incontinent of urine. On day 6 of hospitalization, the patient refused to follow verbal commands. He also refused medication. He was able to understand and respond to questions appropriately but was slow in his responses.
On the seventh hospital day, the patient began hearing voices, having thought-blocking and demonstrated disorganized behaviors and thinking. He was also delusional, stating that his conversations with the psychiatrist were being recorded and played on the hospital's television. He was diagnosed with drug-induced psychotic disorder with delusions and cannabis abuse and prescribed 1 mg risperidone.
By the eighth day of hospitalization, most of this delirium had cleared. The patient was attentive to conversations, but still struggled with attention testing. On the following day (day 9), the patient was examined, released, and returned to duty.
Follow-Up
Upon discharge, the patients’ chain of command and fellow soldiers noted little improvement. The patient was monitored not only because of concerns about a drug relapse, but also due to concerns about ability to self care. The patient required direct supervision to engage or initiate basic daily living tasks. One noncommissioned officer noted that, “the soldier will engage in tasks however, we have to ask or tell him to start it … once he starts he's okay. We need to lay out clothes for him. We need to ask ‘Do you need to go to the bathroom?’ otherwise he will sit there at the [front] desk for hours and not move.”
The patient's negative symptoms along with, disorganized behavior and speech, persisted despite abstinence from any substances for over 2 months. He was subsequently diagnosed with schizophreniform disorder. Three months following initial onset, however, his psychotic symptoms and functioning seemed to improve. The patient's case was referred for military medical review, and it was determined that the patient did not meet criteria to remain in the military. He was returned to his home on the West Coast. Three months later, the patient died in a motor vehicle accident when his vehicle rolled over approaching a curve. He was not wearing his seatbelt.
Discussion
The appearance of various “herbal highs” known collectively as Spice—herbal mixtures whose contents may vary from innocuous, nonpsychoactive vegetable matter to synthetic chemicals with marked psychoactive properties—poses a range of difficult treatment issues for providers.
Smokable herbal mixtures under the name Spice are known to have been available since at least 2004. Often sold over the Internet and in various specialized tobacco shops, Spice is often marketed as an “herbal incense”; however, some brands are marketed as “herbal smoking blends.” In either case, the product is usually smoked.
Synthetic cannabinoids were initially developed in the 1960s at Hebrew University, 1970s by Pfizer, and 1980s by Dr. J. W. Huffman, a researcher at Clemson University. Synthetic cannabinoids first appeared in Europe. Originally sold as “Spice” by a London company called “The Psyche Deli,” the substance has continued to rise in popularity. The term Spice eventually came to refer generically to all herbal mixtures with synthetic cannabinoids added to them. A 3-g bag sells for about $30 to $40.
When synthetic cannabinoid blends first went on sale in the mid-2000s, it was thought that they achieved an effect through a mixture of legal herbs. Laboratory analysis from Germany and Austria in 2008 showed that this was not the case, and in fact contained added synthetic cannabinoids that act on the body in a similar way to cannabinoids naturally found in cannabis, such as tetrahydrocannabinol (THC). A large and complex variety of synthetic cannabinoids, most often cannabicyclohexanol, JWH-018, JWH-073, or HU-210, are used in an attempt to avoid the laws that make cannabis illegal, making synthetic cannabis a designer drug (1).
Although synthetic cannabinoids do not produce positive results in drug tests for cannabis, it is possible to detect its metabolites in human urine. The synthetic cannabinoids contained in synthetic cannabis products have been made illegal in many European countries (2). Responding to similar potential health concerns, the US Drug Enforcement Agency announced that effective 25 December 2010, it would make 5 synthetic cannabinoids Schedule 1 drugs. Prior to the announcement, several US states had already made them illegal under state law (3).
The pharmacology of cannabis and THC, the main psychoactive ingredient of the plant, as well as the human body's endocannabinoid system is well documented (4). In 1958, Ames was the first to document cannabis psychosis in an experimental design with 10 subjects that demonstrated psychological symptoms such as severe anxiety, panic attacks, paranoid delusions, and depersonalization (5). Talbott and Teague in 1969 described 12 US soldiers in Vietnam who had disorientation and hallucinations after their first use of cannabis (6). In Germany, 19 cases of toxic psychosis were reported after hashish use (7), and in Calcutta, Chopra and Smith described retrospectively 200 patients hospitalized after the ingestion of large dose of cannabis between 1963 and 1968 (8).
Little is known about the metabolism and toxicology of Spice synthetic cannabinoid compounds. Furthermore, it cannot be assumed that the risks associated with the use of synthetic cannabinoids are comparable to those seen with THC; indeed, as this case demonstrates, there is reason for concern that these drugs may have a greater potential to cause harm. Moreover, because of the lack of information on synthetic cannabinoid experience, and synthetic cannabinoid dose intake, the interaction between other compounds, and prior psychiatric comorbidity, further studies to assess these risks reliably are needed.
Given that there is little known about Spice, accidental overdosing with a risk of severe psychiatric complications may be more likely to occur because the type and amount of cannabinoid may vary considerably from batch to batch even within the same product. Furthermore, it seems that tolerance to these synthetic cannabinoids may develop fairly fast, and arguably this might be associated with relatively high potential to cause dependence. Without additional studies, it remains unclear if this patient's protracted symptom presentation reflects a substance-induced delirium from a toxin with an extended half-life versus a delirium secondary to acute metabolic withdrawal.
Footnotes
Acknowledgments
This article is not subject to U.S. copyright law.
The views presented are those of authors, and do not represent the values or policies of the Department of Defence.