A CASE OF PHENIBUT DIRECTED DETOXIFICATION LEADING TO TOXICITY DURING THE COVID-19 PANDEMIC

Abstract

Background

Phenibut is a non-Food and Drug Administration-approved gamma-aminobutyric acid analog marketed in the United States as an anxiolytic, cognitive enhancer, and alcohol withdrawal treatment through online supplement vendors. In this case report, we describe a woman’s self-directed detoxification with phenibut used to manage withdrawal symptoms from fentanyl and benzodiazepines in March 2020 during the height of the COVID-19 pandemic.

Case

A 38-year-old woman with severe opioid, benzodiazepine, gabapentin, stimulant use disorders developed altered mental status after oral phenibut ingestion intended to help self-manage opioid and benzodiazepine withdrawal. She chose self-directed detoxification as she feared COVID-19 exposure in detoxification facilities. Her altered mental status drove her to jump out a third-story window causing multiple spinal fractures. After a long hospitalization, she self-directed her discharge home due to concerns about COVID-19. Her premature discharge disrupted opioid and benzodiazepine use disorder treatment plans.

Conclusion

This case highlights the risks of phenibut use for selfdirected detoxification. With COVID-19 related changes in the drug supply, people may be more likely to use online pharmaceuticals, therefore, substance use assessments should inquire about the online acquisition of new psychoactive drugs. Public health messaging regarding the risks of infectious disease transmission in addiction care settings is needed to guide addiction treatment choices among people who use substances.

The novel 2019 coronavirus (COVID-19) pandemic resulted in adaptations and disruptions to addiction treatment and harm reduction services, together with changes in perceptions of safety accessing these services.^1,2 Although data remain limited, case reports are emerging of self-directed detoxification at home among people with substance use disorder (SUD) who fear contracting COVID-19 in detoxification facilities.^3,4 Preliminary data suggested substance use-related emergency department (ED) visits increased during the pandemic, perhaps due to people avoiding detoxification and residential treatment facilities.^3,5,6

Predating COVID-19, people were using the Internet to access drugs and medications for self-directed detoxification.^7,8 Phenibut, a psychotropic substance, first synthesized in the 1960s in Russia, is one such medication that can be purchased online that is gaining popularity in the United States (US).^9,10 Between 2009 and 2019, 1320 phenibut exposures were reported to US poison control centers.¹¹ Research studies, predominantly outside of the US, have described phenibut’s safety and pharmacodynamics. US case reports have reported phenibut intoxication, withdrawal, and addiction.^9,10 However, there remains a paucity of literature on phenibut use for opioid and benzodiazepine detoxification.

Phenibut, a gamma-aminobutyric acid (GABA) analog, is named for its phenyl ring which enhances transmission through the blood-brain barrier compared toGABA.¹⁰ Phenibut functions primarily as a GABAB receptor agonist and stimulates dopamine production and release.¹⁰ Usually phenibut is orally ingested and less commonly used via nasal insufflation and rectal administration.¹² Phenibut is renally excreted unchanged; its plasma half-life is approximately 5.3 hours.^10,13

In Russia, phenibut is prescribed for anxiety, posttraumatic stress disorder, and vestibular disorders.^12,13 Although not licensed for prescription in the US, phenibut can be easily purchased through online vendors, in powder, crystal, and capsule formulations. It is marketed as a nootropic, intended to enhance memory and cognition.⁹ Additionally, it is advertised for fitness endurance, relaxation, and alcohol withdrawal management.¹⁴ On social media forums, phenibut is commonly identified as an alternative treatment for opioid withdrawal.⁷ Here, we describe a case of self-directed detoxification with phenibut for fentanyl and benzodiazepine withdrawal in March 2020 during the height of the COVID-19 pandemic. The patient described below provided consent to publish this case report.

CASE

Ms. T, a 38-year-old cisgender woman, presented to a safety-net hospital’s ED in Boston, Massachusetts for trauma evaluation after jumping out of a third-story window. Two days before her hospitalization, after learning about phenibut from a friend, she purchased phenibut through an online vendor to self-treat anxiety and manage opioid and benzodiazepine withdrawal (Fig. 1). She reported injecting 2 g of fentanyl daily, taking 5–10 mg of nonprescribed clonazepam orally daily, and using up to 2400 mg of nonprescribed oral gabapentin twice daily. Her last use of all substances was 1 day before starting phenibut (Fig. 1).

FIGURE 1.

Timeline of Events. OTP indicates opioid treatment program; PO, by mouth; QID, 4 times daily.

Ms. T had severe opioid, stimulant, gabapentin, and benzodiazepine use disorders. Eight months prior, she had been treated with buprenorphine 16 mg daily which she stopped due to nausea and weight loss. She did not report any overdose events. Her psychiatric history included bipolar spectrum and post-traumatic stress disorders; however, she was not currently taking any prescribed medications. Previously, she had been prescribed escitalopram, quetiapine, and diphenhydramine. There was no history of psychosis, mood instability, or mania. Five years prior, she was involuntarily held in the ED for 3 days due to suicidal and homicidal ideation after a physical assault.

Ms. T ingested several teaspoons of phenibut approximately 2 days before her hospitalization. After her initial phenibut ingestion, she slept for about 24 hours. Her partner, who was supporting her self-directed detoxification, reported that upon awakening she displayed impulsivity, paranoia, and response to internal stimuli by engaging in self-dialogue. Later that day, she was brought to an ED after she left her house without clothes, prompting a 911 call by her partner. She was sent home that same day, but her partner reported that she was still not herself. Once home, she ingested diphenhydramine and additional phenibut (quantity unknown). After these ingestions, she slept briefly and again became aggressive and impulsive. Ms. T ended up jumping out of a thirdstory window, despite her partner’s efforts to pull her back in. She could not remember the motivation for jumping but did not intend to harm herself.

On presentation to the safety net hospital, Ms. T reported difficulty ambulating with severe electric pain radiating down her spine. Her physical exam was remarkable for thoracolumbar tenderness, mydriasis, and decreased hip and knee flexor strength. Imaging demonstrated severe spinal stenosis with unstable T12 and L1 fractures for which she underwent emergent neurosurgery. Urine toxicology was positive for fentanyl and benzodiazepines. Phenibut was undetectable on the standard hospital immunoassays.⁹ A urine sample was not sent for liquid chromatography/mass spectrometry analysis. Treatment was directed based on the patient’s report of phenibut ingestion. Her hospital course was complicated by altered mental status and withdrawal requiring ketamine, dexmedetomidine, propofol, and remi-fentanil while intubated, among anti-psychotics and a 1:1 observer for safety after extubation (Table 1). On hospital day 4, her mental status improved, and she had no persistent symptoms of psychosis; the inpatient addiction service was consulted for SUD management.

TABLE 1.

Pharmacotherapy for Withdrawal and Altered Mental Status

Medications	Dose	Duration
Ketamine	5 mcg/kg/min	9 hours
Dexmedetomidine	1.2 mcg/kg/hr	5 hours
Remifentanil	0.5 mcg/kg/min	8 hours
Propofol	200 mcg/kg/min	9 hours

Through shared decision making, Ms. T started methadone for opioid use disorder with plans to continue at a local opioid treatment program. Before initiating methadone, she reported abdominal pain, headache, diaphoresis, lacrimation, restlessness, myalgia, and anxiety. Yawning, mydriasis, and tachycardia were observed. On subsequent assessments, methadone dosing was titrated to abate opioid cravings. For benzodiazepine withdrawal management, a 3-week diazepam taper was established. Her ongoing anxiety was multifactorial but suggestive of protracted opioid and benzodiazepine withdrawal.

After this traumatic experience, she planned to discard the remaining phenibut at her home. A short-term stay at a physical rehabilitation center was recommended. Due to fear of COVID-19 exposure, Ms. T self-directed her discharge home. Leaving the hospital expeditiously impacted her ability to continue the longer-term benzodiazepine taper. After discharge, she did not present to the opioid treatment program. The day after discharge, she contacted the hospital social worker seeking SUD treatment resources and followed up with neurosurgery 9 days later experiencing severe pain; however, she was initially denied pain medications due to her self-directed discharge.

DISCUSSION

This case report describes phenibut intoxication as an unintended consequence of phenibut use to self-manage fentanyl and benzodiazepine withdrawal. Phenibut intoxication and overdose symptoms include psychomotor agitation, seizure, delirium, dissociative states, hallucinations, decreased consciousness, and stupor.¹⁵ Although phenibut vendors warn against large amounts of initial phenibut use or use for multiple consecutive days, the delayed onset of action of 2–4 hours often leads first-time users to consume more than recommended.^12,16 Acute pain coupled with opioid, benzodiazepine, and gabapentin withdrawal added to Ms. T’s clinical complexity. An interaction between phenibut and diphenhydramine (a known deliriogenic anti-cholinergic) may have also contributed to altered mental status precipitating her serious traumatic event.

This case highlights the risk of phenibut use for self-directed detoxification. Until 2019, phenibut was classified as a dietary supplement in the US. In 2020, the Food and Drug Administration deemed this labeling inappropriate, but like many psychoactive substances (eg, kratom), phenibut can be legally marketed as a nondietary ingredient.^17,18 Although online phenibut vendors include legal disclaimers emphasizing it is not Food and Drug Administration-approved and consumers agree to any potential risks, they often fail to explain risks associated with phenibut use in terms understandable to the public.¹⁹ Healthcare providers caring for people who use substances should routinely inquire about the online acquisition of psychoactive substances when obtaining a substance use history.

This case exemplifies the additional challenges posed by the COVID-19 pandemic for people who use substances at risk of withdrawal. A Canadian study documented how changes in the drug supply including increased costs and decreased access, led some people to substitute, decrease, or stop using their preferred substance.²⁰ Ms. T felt forced to choose between self-directed detoxification or risk COVID- 19 exposure at a detoxification facility. She believed the former to be safer and further chose to forego physical rehabilitation to reduce her COVID-19 risk. Her case exemplifies the valid and intense fear people who use substances experienced during the COVID-19 pandemic.

Ms. T’s case also demonstrates the risks of self-directed detoxification, especially for those using multiple substances. Transparent public health messaging on COVID-19 risks and current protocols to reduce risks within addiction treatment facilities are needed. Such tailored public health messaging can help people who use substances at risk of withdrawal make informed healthcare decisions. Healthcare providers caring for people who use substances should inquire about COVID-19 infection concerns and review COVID-19 risk reduction strategies in addiction care settings, ranging from harmreduction to detoxification and residential treatment services.

CONCLUSIONS

Though reports of phenibut use in the US are increasing, this case highlights the serious risks associated with its use especially in the setting of complex withdrawal syndromes. Healthcare providers caring for people who use substances at risk of withdrawal should obtain comprehensive substance use histories that include inquiries about the online acquisition of new psychoactive substances. During the present and future public health crises, tailored messaging regarding the risks of infectious disease transmission in addiction care settings are needed to guide addiction treatment choices.