Management of GHB/GBL Drug Overdose and Withdrawal Syndrome (Steinberg 3/2022)

Thanks so much to Dr. Gabrielle Steinberg for her excellent presentation on Atypical Addictions: GHB/GBL Drug Overdose and Withdrawal

A recording of Dr. Steinberg's excellent presentation is available HERE. 

We know that addiction is a huge problem worldwide

• Globally, 33.6 million people suffer from substance use disorder (2019)
• In the US between 1999-2020, 841,000 people died  from drug-related overdose
• Synthetic opioids are main driver for SUD related deaths (esp. fentanyl right now)
• In 2011, Drug Abuse Warning Network (DAWN 2011) reported 2.5 million drug use/misuse related ER visits, more than half from multiple drugs: alcohol, cocaine, marijuana, opioids, methamphetamines
• Atypical/uncommon drugs comprise about 5% of ER visits
• GHB/GBL was associated with 2, 406 ER visits in 2011 (US)
• Other "atypical substances": inhalants/solvents, bath salts, Khat, K2/spice, Kratom, U47770, Rohypnol, DMT, MPTP

GHB=gamma hydroxybutyrate

GBL= gamma butyrolactone 

GBL is a precursor to >> GHB is a precursor to>> GABA

GHB is a CNS depressant, also has effect on mesolimbic pathway (rapid reward, abuse potential)

Initially developed in  France as general anesthetic (not in US), can be prescribed in salt form (prescription rx approved to tx narcolepsy, cataplexy). In 1980s, marketed as supplement for body builders, removed from the market due to fatal intoxications/overdose

GHB= schedule 1 (no current recognized medical use, high potential for abuse)

When used illicitly, GHB is used for calming, euphoric effects, aphrodisiac (increases libido).

Considered similar to MDMA/alcohol. 

Also "date rape drug" because of effects on memory and consciousness

• colorless odorless liquid, or white powder that can be dissolved
• mostly ingested orally as liquid, sometimes pill form
• onset: high 15-30 minutes, duration 3-6 hours, doses vary
• tolerance and dependence does build quickly
• death has been associated with overdose, withdrawal and intoxication 

Demographic & use patterns: majority male, majority white, late 20s/30s (same in ED overdose data, though increasing rates GHB overdoses in women), commonly co-ingested with alcohol

GBL now becoming more common than GHB, cheaper, easier to access: found in solvents, greater potency, faster onset

GHB/GBL intoxication

CNS depression, agitation, seizures

Hypothermia, bradypnea, bradycardia (hypotension less common), urinary and fecal incontinence

death from intoxication/overdose can be caused respiratory depression and/or respiratory arrest, aspiration (due to risk for vomiting)

Common to see alternating ABRUPT onset somnolence and agitation

Toxicity can come on and resolve abruptly, effects last 2-5 hours

Hospital stays can be often short because of short half life (managed out of ER and then discharged)

Most of the time GHB/GBL used with other drugs (ETOH, methamphetamines)

Not detected on typical urine drug screen, do have a send out confirmation test (urine test takes 9-10 days to result)

Key to management GHB intoxication: supportive care, airway support (intubation to protect airway when sedated), use of sedation due to abrupt alertness that can occur (midazolam, propofol), best effects with benzos (lorazepam or diazepam) or Haldol

There is no antidote, no effect from naloxone or flumazenil

GHB/GBL withdrawal

Happens quickly, as early as 6 hours after last dose

Mild/mod: anxiety, tremor, diaphoresis, tachycardia

Severe: agitated delirium, seizures, hypothermia, rhabdomyolysis

Preferred treatment: benzodiazepine (PO valium for longer duration), baclofen TID has been studied (shown to reduce withdrawal, reduce cravings, GABA b receptor agonist, small studies)

For severe withdrawal: intubation, IV valium benzo of choice. Can get benzo resistance (acts more on GABA-A receptors). Add on Propofol, Precedex.

Vitamins: magnesium, folate (some Wernicke's like syndrome)

Fluid resuscitation: vomiting, diaphoresis

No validated withdrawal scale, most literature uses CIWA scores

Netherlands study (450 patients): giving GHB taper in the hospital, taper down and off, relatively effective

Belgium tried similar protocol with benzos (less effective)

Outpatient management of GHB/GBL

GHB/GBL use is associated with high risk of abuse, rapid onset of euphoric and calming effects

outpatient labs: GHB urine drug screen is available via Quest labs/ECW (send out, takes some time)

GHB/GBL addiction hard to treat outpatient

Study from Netherlands (596 pts): high rates of relapse with GHB use, withdrawal severity, ER visits, duration of time in treatment programs

Baclofen has been found to be helpful w/detox, but also in maintaining abstinence, no RCTs; one non-RCT found baclofen 45-60mg/day  (10-20mg TID, titrate by patient) PLUS CBT more effective in reducing craving, anxiety, and relapse (than CBT alone). Baclofen decreases need for benzos

Key to outpatient management is wrap around support with interdisciplinary team: more success with patients with lower daily dose. 

Outpatient Rx should include: baclofen PLUS valium/diazepam (symptom guided) PLUS close follow-up PLUS simultaneous behavioral therapy

For help/assistance with these atypical drugs, consider reaching out to the UCSF Substance Use Disorder Warmline https://nccc.ucsf.edu/clinical-resources/substance-use-resources/

855-300-3595.