New-Onset Prolonged Psychosis Following Synthetic Cannabinoid Use in an Older Patient: A Case Report

Abstract

Synthetic cannabinoids (SCs), a class of new psychoactive substances (NPS) commonly known as “spice,” has rapidly gained popularity and become the most ubiquitous NPS on the illegitimate drug market. SCs, unlike natural cannabis (NC), are not controlled by international drug conventions, posing a significant risk to public health. These substances are easily accessible, relatively inexpensive, and challenging to detect in routine drug screenings. The existing literature provides strong evidence of an association between NC use and psychosis, but there is significantly less data on SC psychosis. We present a clinical case report of a 51-year-old African American female with no known psychiatric history who was admitted to the inpatient psychiatric unit after reported paranoia and altered mental status for the preceding six days. During hospitalization, she exhibited disorganization, persecutory delusions, extreme agitation, and bizarre behaviors that included the concealment of a set of stolen keys in her vagina, necessitating an ethics consult. After consideration of differentials, the patient was diagnosed with substance-induced psychotic disorder secondary to SC. The patient was stabilized on 3 mg Risperidone at bedtime. After 16-day hospitalization, she reached her baseline and later revealed that she had recently smoked SC for the first time. The primary goal of this case is to highlight the sequelae of SC-associated psychosis. A SC-associated psychosis could drastically vary from NC and is often undetectable on a typical UDS, which may result in a lifelong primary psychotic disorder misdiagnosis.

Introduction

The current literature provides strong evidence of a significant association between cannabis use and psychosis.^1–3 Synthetic cannabinoids (SC), a new class of psychoactive substances (NPS) most commonly known as “spice” or various other slang names (K2, Genie, Yucatan Fire and King Krypto), has rapidly gained popularity and become one of the most ubiquitous psychoactive substances in the illegal drug market.⁴ Synthetic cannabinoids pose a significant risk to public health as these substances are easily accessible through the internet, convenience stores, and “head shops,” relatively inexpensive, and challenging to detect in routine drug screenings.⁵ Manufacturers of these products evade legal restrictions on marijuana products by modifying the existing chemical structures just slightly such that the product is no longer considered illegal.

SC acts as a full agonist at cannabinoid receptors (CB1 and CB2), exhibiting greater potency compared to tetrahydrocannabinol (THC), the main psychoactive component of the natural cannabis plant (NC).⁶ Dysregulation of the dopaminergic system, along with the interaction between SC, and the GABAergic and glutamatergic systems, plays a role in the development of SC-induced psychosis.⁷ The epidemiological evidence demonstrates a potential correlation between cannabis use, both in the form of SC and NC, and the development of psychotic disorders, particularly schizophrenia.⁸ Cannabis users have a significantly higher risk of developing intractable psychosis compared to non-users, with SC use associated with even greater risks.^1–3 While THC is a partial agonist with a weak affinity for the CB1 receptor, SC is a full agonist and generally has a stronger affinity. Additionally, SC poses a greater overall health risk than NC.^9,10 A survey of 80,000 drug users showed that those who used SC were thirty times more likely to end up in an emergency unit than users of NC.¹¹ Acute physical reactions include nausea and vomiting, breathlessness, hypertension, tachycardia, chest pain, and occasionally acute renal failure. All cannabis-associated psychosis, including SC-induced psychosis, is characterized by early onset, positive symptom predominance, and poorer treatment outcomes.^12–14 We present a 51-year-old patient who presented with profound psychosis without insight following the use of SC. The primary goal of this case is to describe the presentation and course of the psychosis in an older patient with no previous psychiatric history, which originated at the time she switched from NC to SC products. There has been a paucity of data analyzing the use of SC in elderly patients, as most SC users are reported to be young patients.¹⁵

Case Report

Ms. A., a 51-year-old black woman with no past psychiatric history, was admitted to the psychiatric unit after presenting to the emergency department with six days of new-onset paranoia and altered mental status. Upon initial psychiatric assessment, Ms. A. was angry and irritable with congruent affect. She was exhibiting illogical, circumstantial thinking and was extremely paranoid and delusional. Her speech was coherent with normal rate and volume. She believed that she was in jail and continually requested to call her lawyer. She was uncooperative with the care team due to her delusion that they were part of a conspiracy against her. She also described vivid persecutory delusions that two individuals were stealing her phone records and “out to get her”. She denied having a prior psychiatric history and appeared unaware that her behavior was abnormal. Ms. A.’s daughter was contacted to obtain collateral history and corroborated a notable change in her mother’s thoughts and behavior over the past week. Ms. A told her daughter that her family members were evil spirits and that dead family members were alive. On the day prior to the presentation to the ED, Ms. A.’s daughter found her mother throwing documents into the oven and trying to burn the house down on three separate occasions to “get rid of the evidence.” She also complained that people were spying on her and turned off her family member’s cell phones due to concerns for phone tapping. Ms. A was currently in a long-term relationship of nine-year duration. She previously functioned independently (driving, grocery shopping, working at a fast-food restaurant, and paying bills). Ms. A.’s daughter denied a past history of psychiatric illness or autoimmune disease in her mother and was unaware of any substance abuse or sexually transmitted diseases that could have explained her behavioral changes.

Upon admission to the psychiatric unit, the patient intensely resisted wearing clothes despite continuous redirection from the staff prompting the team to place a “no roommate” restriction. On day 1, she began reporting visual hallucinations and attempted to elope from the unit. When the unit staff redirected her, she bit her nurse, prompting agitation protocol. She received 3mg lorazepam and 10mg ziprasidone injections. Initial medical workup included normal EKG, normal CXR, unremarkable CBC and CMP, UA with moderate bacteria and leukocyte esterase, and negative COVID test. The urine drug screen was positive only for cannabis, although the patient denied drug use. She was started on risperidone 1 mg BID. She continued to be agitated and uncooperative over the next few days. On hospital day 4, she required restraints and seclusion as she threw feces and urine at the staff. She consistently refused oral risperidone and was given IM olanzapine 5mg QHS per order to treat obtained from the probate court. On hospital day 5, the patient stole a set of keys from the neck of a staff member. When inquired about the keys, the patient reported that she hid them in her vagina. A bedside ultrasound showed two keys in the pelvic region. The patient denied placing keys in her vagina and refused a pelvic exam. Once it was documented that the patient lacked capacity, gynecology successfully retrieved the keys from the patient’s vagina, and no damage to the vaginal canal was noted. Mrs. A’s medication regimen was increased to 4 mg risperidone nightly and 5mg diazepam three times a day (TID) to address continued agitation. Over the next few days, she was noted to have a gradual improvement in hygiene, irritability, and sociability. She started to become cooperative and had improved insight on hospital day 7. She divulged that she used cannabis “occasionally,” and she met a new dealer who gave her synthetic products about a week before admission. She noted that her cannabis use started affecting her in a negative way beginning at the time she switched to synthetic cannabinoids. Over the course of the hospitalization (day 8-day 15), Ms. A returned to her baseline and exhibited clear, organized thinking, and developed fair insight and judgment into her situation. She was apologetic and embarrassed about her behavior. She was connected to outpatient resources for substance use disorder and counseled on the risk of acute psychosis and rehospitalization. She was amenable to therapy and was set up with an outpatient therapist for regular therapy for psychological issues. Her involuntary petition was dismissed on hospital day 16, and the patient was discharged home on risperidone 3 mg at bedtime and trazodone 50 mg at bedtime as needed for sleep. The patient has not been back to our inpatient unit facility since this incident, and an attempt to get follow-up updates on her via phone was unsuccessful.

Discussion

This case describes a severe and long-lasting first episode, isolated new-onset psychosis following synthetic marijuana use in an older patient with no psychiatric history. Synthetic marijuana is known to have a higher likelihood of severe adverse reactions as the psychopharmacological properties are vastly different from NC despite sharing similar nomenclature. NC contains cannabidiol and is a partial agonist at the CB-1 receptor. In contrast, SC compounds typically do not contain cannabidiol, and most commercial products contain blends of aminoalkylindoles and cyclohexylphenols, which have been shown to be complete agonists at the CB-1 and CB-2 receptors. These structures have also been proven to exhibit significantly higher binding properties proven to exhibit significantly higher binding properties, with some studies citing a binding affinity of over 500x greater than natural cannabis.^16,17 This case elucidates that those who end up hospitalized are often unaware that the product they used was synthetic or different from the plant-based products they are used to. Some confusion about the nature of the product being used is likely because SC is often legally sold in convenience stores, even in states where NC is illegal. Manufacturers are finding creative ways to bypass FDA oversight, such as marketing products as “natural herbal mixtures” and labeled “intended for incense”. Many individuals report choosing SC over traditional delta-9 THC as it is more difficult to detect on drug screens,¹⁸ a likely explanation for why states with restrictive marijuana policies have had higher rates of SC-related toxicology cases.¹⁹

Our patient demonstrated severe adverse psychiatric effects from synthetic cannabis leading to a lengthy hospitalization and during which she exhibited life-threatening hallucinations and delusions that persisted for two weeks. Other reported cases have shown similar protracted presentations that lasted well beyond acute intoxication.²⁰ One case series was shown to have multiple previously healthy young men who exhibited new-onset psychosis with symptoms that persisted for multiple months after the initial inciting event.²¹ Uniquely, our patient was older than those presented in previously published reports, indicating a potentially high risk of psychosis from SC use for any age group, including patients who are long past the age when primary psychotic disorders typically present. Although she reported longstanding use of NC premorbidly, she had been functioning well and only presented with psychotic symptoms after using SC. Our clinical observation of the prolonged and severe nature of psychotic episodes in patients with no previous psychiatric history who were diagnosed with SC-induced psychosis is drastically different from the cases we have seen of NC-induced psychosis, as exemplified by this case. While there have been more aggregate NC-related ED visits on average, the course of patients presenting with NC-induced psychosis has been noted to be far shorter, less severe, and with fewer positive symptoms at our institution. One hypothesis that has gained prominence is that cannabinoids in NC have been shown to exhibit antipsychotic properties, as small-scale clinical studies with CBD treatment have shown promise in patients with psychotic symptoms.²² This could be a likely explanation for why we have seen less pronounced psychotic features in patients with first-episode psychosis induced by NC as opposed to SC. Limitations of this case study include not having a chemical sample of what the patient consumed to prove the synthetic nature, but it is highly likely from her report of changing products.

Conclusion

This case depicts a 51-year-old black female with no previous psychiatric history who developed profound psychosis with prominent persecutory delusions, disorganized speech, and behavior following reported SC use. The symptoms eventually resolved after initiating an atypical antipsychotic at a moderate dosing level. It is imperative that clinicians become aware of the presentation of SC-associated psychosis and routinely screen historically and by laboratory measures for the use of SC when an unusually severe case of psychosis presents at any age, particularly when the presentation is atypical for the individual. Moreover, when a history of recent SC use is determined to be related temporally to the psychosis presentation, clinicians should consider utilizing antipsychotics early in treatment, with a low threshold for dosage escalation. Education of patients about the risks of marijuana, and especially SC, is valuable. Larger comparative and cohort studies are needed to further guide the diagnosis and treatment of these toxic agents.