Spice Detox - Abbeycare

Home
Spice
Spice Detox

Jump To:

KEY TAKEAWAYS

Symptomatically treating spice withdrawal symptoms (e.g. existential panic, hypertension, i.e > 140/90 mmHg) with medication as needed (e.g. 40mg propranolol) for 7 days
Stabilising CB1R/CB2R, dopamine, noradrenaline, and glutamate signalling after being overstimulated or suppressed by spice during active use

Below, we discuss possible approaches that meet the specific detox needs around spice. Not all treatment centres will provide these specific interventions.

For an overview of the Abbeycare programme contents for spice detox, click here.

Spice Detox Symptom Management

There is no medicated detox available for spice, and symptom management protocols including beta-blockers (e.g. 10mg propranolol), benzodiazepines (e.g. 10mg diazepam), and antipsychotics (e.g. 50mg quetiapine) are used for ≤ 7 days during an inpatient detox to [1]:

Control anxiety, panic, profuse sweating, and palpitations developing within 24 – 48 hours of cessation by inhibiting beta-1 and beta-2 adrenergic stimulation in the heart, although propranolol is avoided in patients with bradycardia (HR = < 60 BPM)
Manage restlessness, agitation, and sleep disturbances (i.e. nightmares, vivid dreams) that peak around 72 hours after last using spice, by binding to GABA-A and 5-HT2A receptors to regulate mood by minimising neuronal excitability

10mg Metoclopramide is administered every 4-6 hours during treatment for spice addiction to mitigate nausea in 30% of patients who previously used 3g a day for 2 years, often developing within 1 hour of last use, peaking during day 2, and subsiding by day 7 [1][2].

The Cannabis Withdrawal Assessment Scale is used during spice rehab to establish the severity of symptoms (e.g. sweating) in the preceding 24 hours using a scoring system (e.g. 3 = severe), and medication is adjusted as needed (e.g. 10mg to 40mg propranolol) [1].

Physical Symptoms Of Spice Detox

Gastrointestinal Cramping

Gastrointestinal cramping is a physical spice withdrawal symptom because cholinergic contractions are no longer inhibited by 77% due to the downregulation of CB1 receptors in the enteric nervous system (ENS), leading to [3]:

A loss of appetite in 43% after discontinuing heavy spice use (e.g. around 2.8g a day) due to abdominal cramps, vomiting, nausea, and epigastric pain for up to 7 days after cessation [2][4]
Some patients claim, “When I quit smoking, I struggle to eat an apple, I vomit more than I urinate, and I have diarrhoea every third hour,” due to the dysregulation of smooth muscle relaxation, gut motility, and the secretion of digestive fluids [5]

Hopkins & Gilchrist (2013) studied a 30-year-old who no longer experienced “severe crampy abdominal pain” with intractable nausea and vomiting within 14 days of abstaining from spice and taking ondansetron, after previously smoking every hour during active use [6].

Abdominal cramps are treated with 20mg Hyoscine Butylbromide for up to 7 days during spice withdrawal, and nurses encourage patients to maintain hydration (e.g. 2L of liquids daily) and eat regular light meals to manage nausea and dehydration after vomiting [1].

Uncontrollable Tremors

Uncontrollable tremors are physical spice withdrawal symptoms because the sympathetic nervous system becomes overactive as noradrenaline rebounds after being suppressed by 27 - 50% in the cerebral cortex, cerebellum, and hippocampus during active use [7].

Uncontrollable tremors typically last 3 – 4 days and are exacerbated by motor instability caused by a 62% decrease in dopaminergic activity within 24 hours of abstaining from spice, after being elevated by up to 150% while actively using up to 10g a day [8][9][10].

Zimmermann et al. (2009) studied a 20-year-old man who developed tremors with “electrical shocks” and “twitches” on the 4th day of spice abstinence after using 3g daily for 8 months, subsiding by day 7 after taking 25mg Promethazine and 0.175mg Clonidine [11].

Nacca et al. (2013) studied a 20-year-old man who presented with tremors on the 6th day of spice cessation, after 18 months of daily use, alleviated by taking 50mg Quetiapine daily due to the stabilisation of dopamine and serotonin levels in the brain [12].

Seizures

Seizures are a physical withdrawal symptom because the 46% CB1R-mediated inhibition of hippocampal glutamate release is reversed due to the desensitisation of the endocannabinoid system (ECS) during detox [13].

8% of spice users have seizures after smoking the drug up to 4 times a day, as using synthetic cannabinoids increases the risk of having a seizure by 3-fold due to imbalances in excitatory (e.g. glutamate) and inhibitory (e.g. GABA) neurotransmission in the brain [14][15]:

Havenon et al. (2011) investigated a 24-year-old man who experienced a 3 – 5-minute generalised tonic-clonic seizure after taking spice, followed by a 1-minute seizure with urinary incontinence and postictal confusion later that day [16]
Schep et al. (2015) studied a 23-year-old spice user who had 2 generalised tonic–clonic seizures within 4 - 6 hours of last use, leading to urinary incontinence and tongue lacerations, although seizure activity stopped within 12 hours of taking diazepam [17]

Some spice users have seizures within 2 hours of last use, and others have recurrent seizures after day 1, although anticonvulsants (e.g. Fosphenytoin 15mg/kg) and barbiturates (e.g. 100mg Phenobarbital) are used during treatment to control convulsions as needed [18].

Abbeycare conducts regular observations (e.g. every 15 - 30 minutes) for patients at risk of having seizures during spice withdrawal, and each single-occupancy room includes emergency pull cords to alert nurses if necessary.

Hypertension

Hypertension (BP ≥ 140/90 mmHg) is a physical K2 withdrawal symptom because the sympathetic nervous system becomes overactive due to disruptions in CB1R signalling, leading to dizziness, blurred vision, headaches, and chest pain in up to 68% of patients [15].

Zimmermann et al. (2009) investigated the case of a 20-year-old man who experienced hypertension during a detoxification from spice after previously consuming 1-3g daily for around 8 months:

Headaches and feelings of numbness in the right arm and fingers lasting around 1 minute each time developed as blood pressure reached a maximum of 180/90 mmHg on the 4th day of abstinence
Blood pressure remained elevated at 140/90 mmHg (normal values = 90/60 - 120/80 mmHg) until the 21st day of treatment and gradually stabilised after taking 0.175 mg clonidine [11]

Nacca et al. (2013) found that blood pressure stabilised at 106/58 mmHg by the 6th day of spice cessation, although chest pain, dyspnea, palpitations, and headaches remained due to tachycardia (HR = 120 BPM) in a 20-year-old ex-daily user [12].

Psychological Symptoms Of Spice Detox

Paranoid Ideation

Paranoid ideation is a psychological spice withdrawal symptom because within 1 day of cessation, dopamine levels drop by 15 - 62% in brain regions (e.g. lateral temporal cortex, hippocampus) responsible for sensory integration and context processing, leading to [8]:

Paranoia with “intense fear” in 9%, as some patients claim to have been ‘wiretapped’ by intelligence agencies (e.g. MI5) using ‘special equipment’ (e.g. inductive coil taps) from the 3rd day of spice withdrawal [19]
Excessive suspiciousness and paranoia about imaginary threats after 24 hours of last abusing spice, as one patient claimed, “I believed there were spiders behind me wherever I went” [5]

Paranoid ideation typically lasts 10 – 14 days after the last use of spice, and is exacerbated in 30% of patients who develop paranoid schizophrenia after drug-taking, leading to severe paranoia, agitation, and persecutory delusions within 72 hours of cessation [19][20].

Antipsychotics (e.g. 7.5mg Haloperidol) are administered on a case-by-case basis to mitigate paranoia and delusions (e.g. thoughts about being targeted by drug traffickers) during the first week of the synthetic cannabinoid detox process [20].

Night Terrors

Night terrors are a psychological K2 withdrawal symptom caused by the rebound of REM sleep after being suppressed by spice, exacerbated by neurochemical imbalances (e.g. a 62% decrease in hippocampal dopamine) within 24 hours of cessation [8]:

53% experience sleeplessness during withdrawal due to a 3-fold increase in spells of terror and panic, thoughts of death, and becoming suddenly scared compared to natural cannabis users, after using up to 3g a day for 2+ years [2][21]
Zimmermann et al. (2009) studied a 20-year-old who slept < 5 hours a night after having nocturnal nightmares and sweating profusely during days 4 - 18 of withdrawal, despite claiming to “sleep so well” whilst previously using up to 4g of spice daily [11]

Craft et al. (2022) found that sleep issues (e.g. night terrors) were the most common (59%) symptom reported after abstaining from spice for ≥ 1 day, and for every extra gram of spice taken during active use, the severity of withdrawal increased by 13% [22].

If required, benzodiazepines (e.g. 5-10mg Diazepam) or Z-drugs (e.g. 7.5 - 15mg Zopiclone) are administered at bedtime to control night terrors by stimulating GABA in the brain to promote sleep and relaxation during a medically managed spice withdrawal [1].

Cognitive Disorganisation

Psychomotor slowing, described by patients as “getting stuck”, is a psychological withdrawal symptom that typically occurs within 1 – 2 days of detoxing from synthetic cannabinoids, and in some cases lasts up to 18 months because [19]:

Dopamine is reduced by up to 62% in the lateral temporal cortex and hippocampus within 24 hours of cessation, resulting in thought blocking and memory loss due to impaired semantic processing, thought integration, and memory contextualisation [8]
Chronic spice use (e.g. 1 – 7g daily for up to 12 years) leads to a 37% reduction in executive functioning (e.g. ability to organise thoughts or inhibit responses), causing patients to feel "mentally sluggish" and "absent-minded" after cessation [5][24]

Roberto et al. (2016) found that cognitive disorganisation resolved within 14 days of spice abstinence and daily Risperidone treatment in an 18-year-old male who initially presented with slowed cognition, thought-blocking, and disorganised speech after daily use [25].

Existential Panic

Experiencing a “hazy existence” marked by apathy and depersonalisation is a psychological symptom of K2 detoxification because 50% of patients have high levels of dissociation (DES score > 30) after long-term use (12+ months), resulting in [5][26]:

Feeling “disconnected from life” within 24 hours of last taking spice, as some patients become distressed after claiming, “It’s like losing the magic of life, the thing that makes me feel animated, soulful and having a personality.” [5]
Alterations in perception (e.g. dissociation from reality, hallucinations) in 68% after previously consuming spice up to 4 times a day, as some patients claim “Time felt 3-times slower than normal, as if space and time were altered” during withdrawal [4][15]

Dadi et al. (2016) studied a 20-year-old man who experienced depersonalisation for 17 months after abstaining from spice, resulting in emotional numbing, the impression of “being in a dream”, and detachment from the body, thoughts, and feelings [27].

Existential panic contributes to anxiety, restlessness, and panic attacks in up to 67% of patients during spice withdrawal, and beta-blockers (e.g. 40mg propranolol) are provided to alleviate palpitations, sweating, chest pains, and shaking if necessary [2].

Spice Detoxification Vs Cannabis Detoxification

	Spice Detox	Cannabis Detox
Pharmacological Action	Downregulation of the endocannabinoid system after spice acts as a full agonist at CB1/CB2R Striatal dopamine decreases by 20% within 1 day [9]	Desensitisation of CB1R + CB2R after THC acts as a partial agonist Striatal dopamine decreases by 18% within 5 days [28]
Withdrawal Onset	≥ 1 hour [1]	24 - 48 hours [1]
Withdrawal Duration	Around 7 days (peaks on day 2); depersonalisation may last up to 17 months [1] [27]	7 - 14 days (peaks between days 2 - 5); depersonalisation may last 6 - 10 months [1][29]
Risk Of Psychosis?	Increased by 11-fold [30]	Increased by 3-fold [30]
Psychological Symptoms	Existential panic, cognitive disorganisation, paranoid ideation, night terrors	Anxiety, restlessness, irritability, low mood, insomnia
Medical Complications	Seizure risk = Odds Ratio: 2.90 [14] 30x more likely to need emergency treatment than cannabis patients due to cardiotoxicity [31]	Seizure risk = Odds Ratio: 0.65 [14] Cannabinoid Hyperemesis Syndrome
Symptom Management	Beta-blockers (e.g. 40mg Propranolol), Anti-psychotics (e.g. 25mg Quetiapine), Benzodiazepines (e.g. 10mg Diazepam)	Z-drugs (e.g. 10mg Zolpidem), NSAIDs (e.g. 600mg Ibuprofen), Anti-sickness medication (e.g. 10mg Metoclopramide)

Spice Detox Positive Markers

Improved Cognitive Processing

An 11% increase in working memory capacity and attentional control, and a 190 ms increase in cognitive processing speed within 28 days, is a positive marker of spice recovery because synaptic plasticity and long-term potentiation are no longer disrupted by [23][32]:

A 62% decrease in dopamine activity in brain regions (e.g. hippocampus) responsible for memory encoding and spatial learning, occurring within 24 hours of cessation, and stabilising within 6 weeks after previously consuming up to 10g of spice daily [8][9]
A 2-3-fold increase in inflammatory cytokines (e.g. TNF-α, IL1β, IL6) during active spice addiction, leading to excitotoxicity and damage to the brain’s immune cells (e.g. monocytes, microglia) as a result of excessive CB2R stimulation in the CNS [33]
A 3-fold increase in oxidative stress levels caused by the overactivation of CB1 receptors during intoxication, disrupting the prooxidant–antioxidant balance due to the accumulation of reactive oxygen species after misusing spice [33]

Improved Autonomic Responses

A 20 mmHg reduction in systolic blood pressure and a 24% reduction in heart rate (e.g. 125 BPM to 95 BPM) within 48 hours is a positive marker of recovery during spice addiction treatment because [11]:

Tachycardia (HR >100 BPM) and hypertension (BP>140/90 mmHg) subside within 21 days of cessation and treatment with 0.175mg Clonidine due to the regulation of sympathetic outflow after abstaining from heavy spice use (e.g. 1-3g daily) [11]
Body temperature stabilises at 36.7°C within 8 days of abstinence after being increased by up to 41°C and causing profuse sweating during days 4 – 7 as a result of autonomic nervous system dysregulation [7][11][34]

Autonomic responses (e.g. cardiac rhythm) typically stabilise within 5 – 9 days of spice abstinence after becoming irregular within the first 48 hours due to sympathetic hyperactivity caused by the downregulation of CB1 receptors during abrupt withdrawal [19].

Reduction In Anxiety

A 4% reduction in scores on The State-Trait Anxiety Inventory is a positive marker of recovery from spice addiction because patients are no longer “Completely struck by panic” due to the stabilisation of the endocannabinoid system within 4 weeks of cessation [5][23][32].

29% of patients recover from anxiety and panic attacks within 2 weeks of last taking spice, initially triggered by a 31% spike in cortisol following the activation of the hypothalamic-pituitary-adrenal (HPA) axis stress response during abrupt cessation [35][36].

Samaan et al. (2019) studied an 18-year-old ex-spice user whose anxiety subsided within 2 – 3 weeks of discharge from an inpatient facility after experiencing panic attacks, sweating, palpitations, and chest tightness during the first 4 days of withdrawal [37].

Spice addiction treatment programmes manage anxiety and panic attacks in up to 67% by providing a quiet environment with low stimulation to promote relaxation and beta-blockers (e.g. 20mg Propranolol) to control palpitations and sweating [2].

How Does Spice Being Used With Other Drugs Alter Detoxification from Spice?

	Changes in Tapering Rate	Changes In Detox Duration	Detox Assessments
Benzodiazepines	10% reduction every 10 - 14 days	3 - 20+ weeks (depending on starting dose, e.g. 40mg diazepam = up to 5 months)	Clinical Institute Withdrawal Assessment Scale – Benzodiazepines + The Glasgow Coma Scale
Opioids	Buprenorphine (2 - 16mg) tapering regimen for up to 60 days	5 - 10 days for short-acting (e.g. heroin) vs up to 6 weeks for long-acting (e.g. methadone)	Clinical Opiate Withdrawal Scale + Subjective Opiate Withdrawal Scale
Hallucinogens	No taper required + symptomatic treatment (e.g. 100mg Lamotrigine for HPPD)	Around 7 - 14 days	The Drug Abuse Screening Test + Strasbourg Visual Scale + Oral Health Assessment Tool
SSRIs	The current dose (e.g. 100mg sertraline) is reduced by 25% every week	6 - 8 weeks	Severity of Dependence Scale + The Hunter Serotonin Toxicity Criteria
Alcohol	Diazepam/Chlordiazepoxide is tapered over 5 - 7 days (e.g. ≤ 120mg in 24 hours)	Up to 14 days for severe withdrawal (CIWA-Ar score > 20)	Clinical Institute Withdrawal Assessment of Alcohol Scale + Liver and Kidney function (e.g. eGFR, ALT/AST) tests
Ketamine	Up to 250mg of Chlordiazepoxide is tapered over 1 week (case-by-case basis)	Around 10 days	Clinical Institute Narcotic Assessment + Pelvic Pain and Urgency/Frequency Questionnaire

How Does Pre-Existing Schizophrenia Alter Detoxification from Spice?

Pre-existing schizophrenia alters detox programmes for spice addiction because:

Psychosis caused by dopaminergic and glutaminergic abnormalities in schizophrenic patients is exacerbated by disruptions in the endocannabinoid system and D2/D3 receptor binding (-15% in the lateral temporal cortex) during spice withdrawal [9]
Schizophrenic patients are 168% more likely to experience auditory hallucinations compared to the general population, and the addition of spice abuse increases the risk of auditory disturbances by 11-fold [30][38]
12% of patients with paranoid schizophrenia experience delirium within 96 hours of spice cessation, requiring higher doses of antipsychotics (e.g. 5 vs 10mg Haloperidol) to control disorientation, hallucinations, anxiety, and agitation [20]
Detox may last 2 months rather than 7 - 14 days because some schizophrenic patients experience delayed “flashbacks” around 4 – 8 weeks after the onset of spice withdrawal, including pseudo-hallucinations and persecutory delusions [20]

Schizophrenic patients are assessed on a case-by-case basis to establish whether Abbeycare’s spice rehab programme is appropriate, or if psychiatric hospitalisation is required for severely ill (CGI-S > 6) patients; please contact the admissions team for more information.

Spice (K2) Detox At Abbeycare

At Abbeycare, each patient’s detox from spice depends on physical and psychological assessments and decisions made by medical professionals during the 28-day rehab programme, although standard protocols include:

Medically managing withdrawal symptoms (e.g. gastrointestinal cramping, hypertension) with medication (e.g 20mg Hyoscine butylbromide) as needed, retrieved from the nurse's office each day whilst staying in the detoxification wing during week 1
Assigning patients with a keyworker within the first 72 hours of admission and providing an agenda for the following day of treatment (e.g. 7:00 am breakfast, 8:00 am medication) to create structure and ease anxiety during early recovery
Maintaining patient safety by conducting regular observations (e.g. every 30 minutes) and installing emergency pull cords in bedrooms and bathrooms to alert medical staff in the event of severe panic attacks or seizures after withdrawing from spice
Liaising with GPs to discuss treatment options (e.g. antidepressants) for persistent anxiety, sleep disturbances, or psychosis, and referring patients to psychiatric services if appropriate

References

[1] NSW Ministry of Health. Management of Withdrawal from Alcohol and Other Drugs Clinical Guidance. Aug. 2022. Accessed 28 May 2025.“Patients withdrawing from synthetic cannabinoids may experience palpitations, dyspnoea and chest pain. They may have tachycardia and hypertension, ... features may come on quickly following cessation of use, even within an hour, though typically they peak around day two, and last for around one week, ... medication should be supervised (e.g. daily dispensing or supervised by carer) and limited to several days (no more than one week) – corresponding to the peak withdrawal symptoms.”
[2] Umut, Gokhan, et al. “Impact of at Least 2 Years of Synthetic Cannabinoid Use on Cognitive and Psychomotor Functions among Treatment-Seeking Male Outpatients.” Cannabis and Cannabinoid Research, Oct. 2019. Accessed 28 May 2025. “Table 3.”
[3] Grassin-Delyle, S., et al. “Cannabinoids Inhibit Cholinergic Contraction in Human Airways through Prejunctional CB1 Receptors.” British Journal of Pharmacology, vol. 171, no. 11, May 2014, pp. 2767–77. Accessed 28 May 2025.“Δ9-tetrahydrocannabinol, WIN55,212-2 and CP55,940 induced concentration-dependent inhibition of cholinergic contractions, with maximum inhibitions of 39, 76 and 77%, respectively.”
[4] Assi, Sulaf, et al. “Uses, Effects and Toxicity of Synthetic Cannabinoids from the Perspective of People with Lived Experiences.” Journal of Psychoactive Drugs, vol. 52, no. 3, Feb. 2020, pp. 237–47. Accessed 28 May 2025.“Gastrointestinal adverse effects experienced by users included general gastrointestinal irritations, with abdominal pain, abdominal cramps, nausea, vomiting and diarrhoea, ... described as intense, strong and of long duration (up to seven days after smoking).”
[5] Soussan, Christophe, and Anette Kjellgren. “The Flip Side of ‘Spice’: The Adverse Effects of Synthetic Cannabinoids as Discussed on a Swedish Internet Forum.” Nordic Studies on Alcohol and Drugs, vol. 31, no. 2, Apr. 2014, pp. 207–20. Accessed 28 May 2025."Reported experiences showed that users withdrawing from long-term use had trouble tasting food, lost their appetite, ... 'When I quit smoking I struggle to eat an apple, I vomit more than I urinate and I have diarrhea every third hour”.
[6] Hopkins, Christopher Y., and Brandi L. Gilchrist. “A Case of Cannabinoid Hyperemesis Syndrome Caused by Synthetic Cannabinoids.” The Journal of Emergency Medicine, vol. 45, no. 4, Oct. 2013, pp. 544–46. Accessed 28 May 2025.“The patient reported that he would develop severe crampy abdominal pain associated with intractable nausea and vomiting, ... He reported that it took 2 weeks of sobriety before his symptoms completely resolved.”
[7] Moranta, David, et al. “Chronic Treatment and Withdrawal of the Cannabinoid Agonist WIN 55,212-2 Modulate the Sensitivity of Presynaptic Receptors Involved in the Regulation of Monoamine Syntheses in Rat Brain.” Naunyn-Schmiedeberg’s Archives of Pharmacology, vol. 379, no. 1, Aug. 2008, pp. 61–72. Accessed 28 May 2025.“Acute WIN 55,212-2 also reduced the content of noradrenaline in the cerebral cortex (50%), hippocampus (39%), and cerebellum (27%).”
[8] Castaneto, Marisol S., et al. “Synthetic Cannabinoids: Epidemiology, Pharmacodynamics, and Clinical Implications.” Drug and Alcohol Dependence, vol. 144, Nov. 2014, pp. 12–41. Accessed 28 May 2025“A 23-year-old man, admitted to a German inpatient detoxification clinic for SC withdrawal symptoms, ...the patient’s first PET scan showed globally decreased D2/D3 binding, with the lateral temporal cortex and hippocampus least (−15%) and most (−62%) affected.”
[9] Rominger, Axel, et al. “Effects of Acute Detoxification of the Herbal Blend ‘Spice Gold’ on Dopamine D2/3 Receptor Availability: A [18F]Fallypride PET Study.” European Neuropsychopharmacology, vol. 23, no. 11, Nov. 2013, pp. 1606–10. Accessed 28 May 2025.“He progressively increased his daily consumption to 10 g per day, ... cessation evoked severe withdrawal symptoms characterized by anxiety, unstable moods and crying fits, as well as feelings of inner emptiness, spatial disorientation, hyperacusis, somatic pain, shortness of breath and hyperventilation, intense sweating, and sensations of motor and inner restlessness, ... he suffered severe withdrawal symptoms, lasting 3–4 days.”
[10] Ossato, Andrea, et al. “Psychostimulant Effect of the Synthetic Cannabinoid JWH-018 and AKB48: Behavioral, Neurochemical, and Dopamine Transporter Scan Imaging Studies in Mice.” Frontiers in Psychiatry, vol. 8, Aug. 2017. Accessed 28 May 2025.“JWH-018 induced a long-lasting increase of NAc shell extracellular DA levels (~150% of baseline values; Figure 4C), while AKB48 caused a rapid and significant increase in extracellular DA levels in the NAc shell of mice, reaching a peak value (~150% of baseline values) 40 min (Figure 4D) after its administration.”
[11] Zimmermann, Ulrich S., et al. “Withdrawal Phenomena and Dependence Syndrome after the Consumption of ‘Spice Gold.’” Deutsches Ärzteblatt International, vol. 106, no. 27, July 2009, pp. 464–67. Accessed 28 May 2025.“A 20-year old patient reported that he had smoked ‘Spice Gold’ daily for 8 months, ... On hospital days 4–7, he developed inner unrest, drug craving, nocturnal nightmares, profuse sweating, nausea, tremor, ... From the morning of day 7, the symptoms disappeared and the patient felt well.”
[12] Nacca, Nicholas, et al. “The Synthetic Cannabinoid Withdrawal Syndrome.” Journal of Addiction Medicine, vol. 7, no. 4, Apr. 2013, pp. 296–98. Accessed 28 May 2025.“A 20-year-old man presented to the ED, complaining of chest pain, palpitations, dyspnea, headache, diaphoresis, and tremors. He reports the use of 3 g of ‘Mr. Nice Guy’ daily for 18 months, with cessation 6 days before presentation, ... After receiving 50 mg of quetiapine in the hospital setting, he obtained significant relief.”
[13] Hoffman, Alexander F., et al. “Disruption of Hippocampal Synaptic Transmission and Long-Term Potentiation by Psychoactive Synthetic Cannabinoid ‘Spice’ Compounds: Comparison with Δ9 -Tetrahydrocannabinol.” Addiction Biology, vol. 22, no. 2, Jan. 2016, pp. 390–99. Accessed 29 May 2025.“Among the first generation of synthetic cannabinoid compounds isolated from confiscated synthetic marijuana products was JWH-018. JWH-018 inhibited fEPSPs in mouse brain slices, ...The maximal inhibition was 46 ± 7% (n = 5) at 100 nM.”
[14] Wolfe, Caitlin E., et al. “Seizures as a Complication of Recreational Drug Use: Analysis of the Euro-DEN plus Data-Set.” NeuroToxicology, vol. 73, July 2019, pp. 183–87. Accessed 7 Nov. 2019.“Conversely, fentanyl itself remained significantly associated with an increased risk of seizure (OR 2.63, 95% CI 1.20-5.80), as did the synthetic cannabinoids (OR 2.90, 95% CI 2.19-3.84).”
[15] Abdelmoneim, Wafaa M., et al. “Clinical Pattern of Synthetic Cannabinoids Users in Upper Egypt: Cross-Sectional Study.” Middle East Current Psychiatry, vol. 29, no. 1, Mar. 2022. Accessed 29 May 2025.“Table 4 - Symptoms of toxicity or withdrawal experienced after SCs use.”
[16] Havenon, Adam de, et al. “The Secret ‘Spice’: An Undetectable Toxic Cause of Seizure.” The Neurohospitalist, vol. 1, no. 4, Sept. 2011, pp. 182–86. Accessed 29 May 2025.“Case 1 is a 24-year-old male with a history of paranoid schizophrenia and hypertension who presented to the ED after having a witnessed GTC seizure lasting approximately for 3 to 5 minutes followed by a prolonged postictal state, ... After admission, the patient had a second GTC seizure lasting 1 minute with urinary incontinence and postictal confusion. Upon further questioning, he reported smoking ‘funky monkey’ Spice that day.”
[17] LJ Schep, et al. “Delayed Seizure-like Activity Following Analytically Confirmed Use of Previously Unreported Synthetic Cannabinoid Analogues.” Human & Experimental Toxicology, vol. 34, no. 5, SAGE Publishing, Sept. 2014, pp. 557–60. Accessed 29 May 2025.“A 23-year-old male recreationally smoked a synthetic cannabinoid cigarette (trade name K2) at home and 6 h later he suffered what his wife described as generalized tonic–clonic seizure activity, including urinary incontinence and tongue lacerations, ... Three hours after discharge, the patient experienced a second episode of seizure activity.”
[18] Cooper, Ziva D. “Adverse Effects of Synthetic Cannabinoids: Management of Acute Toxicity and Withdrawal.” Current Psychiatry Reports, vol. 18, no. 5, Apr. 2016. Accessed 29 May 2025.“Table 1.”
[19] V. Yu. Skryabin, and M. A. Vinnikova. “Clinical Characteristics of Synthetic Cannabinoid-Induced Psychotic Disorders: A Single-Center Analysis of Hospitalized Patients.” Journal of Addictive Diseases, vol. 37, no. 3-4, Taylor & Francis, Oct. 2018, pp. 135–41. Accessed 30 May 2025.“Overall, four (8.7%) patients had a psychotic disorder in the structure of withdrawal syndrome, ... Patients presented delusional ideas that they were deprived of their will, their actions were imposed from outside, someone was wiretapping them through special equipment (as a rule, it was various intelligence agencies).”
[20] Bokhan, N. A., and G. Yu. Selivanov. “Psychiatric Comorbidity and Synthetic Cannabinoid (Spice) Abuse Syndrome.” Journal of Concurrent Disorders, June 2023. Accessed 30 May 2025.“The primary group of patients with endogenous mental disorders consisted of 140 individuals diagnosed with paranoid schizophrenia (PS) and concurrent addiction to synthetic cannabinoids (F20.хx+F12.2), ... it developed after 3.5 days of abstinence from the use of SC, ...Subsequently, haphazard ideas arose (persecution by participants in drug trafficking, surveillance).”
[21] Mensen, Vincent T., et al. “Psychopathological Symptoms Associated with Synthetic Cannabinoid Use: A Comparison with Natural Cannabis.” Psychopharmacology, vol. 236, no. 9, Apr. 2019, pp. 2677–85. Accessed 30 May 2025.“Table 4.”
[22] Craft, Sam, et al. “Clinical Withdrawal Symptom Profile of Synthetic Cannabinoid Receptor Agonists and Comparison of Effects with High Potency Cannabis.” Psychopharmacology, vol. 239, Sept. 2021, pp. 1349–57. Accessed 30 May 2025.“Withdrawal symptoms after not using SCRAs for >1 day; most frequently reported were sleep issues (59.2%), ... for every additional gram of SCRAs used, the number of withdrawal symptoms increased by around 13%.”
[23] Livny, A., et al. “The Effects of Synthetic Cannabinoids (SCs) on Brain Structure and Function.” European Neuropsychopharmacology, vol. 28, no. 9, Sept. 2018, pp. 1047–57. Accessed 2 June 2025.“Table 2.”
[24] Sant, Kristian. Beyond the Highs of Synthetic Cannabinoids: A Study on Cognitive Function. 2022. Accessed 2 June 2025."Table 14.”
[25] Roberto, Aaron J., et al. “First-Episode of Synthetic Cannabinoid-Induced Psychosis in a Young Adult, Successfully Managed with Hospitalization and Risperidone.” Case Reports in Psychiatry, vol. 2016, 2016, pp. 1–4. Accessed 2 June 2025.“Mr. A exhibited progressive rigidity, intermittent mutism, and cognitive slowing, ... thought blocking, and stuttering, ... He was stabilized over 1.5 weeks on oral risperidone, 2 mg in the morning and 3 mg at bedtime.”
[26] Yücens, Bengü, et al. “The Severity of Dissociative Symptoms among Patients with Cannabis and Synthetic Cannabinoid Use Disorder: Association with Substance Use Characteristics and Suicide.” Psychiatry and Clinical Psychopharmacology, vol. 29, no. 4, Aug. 2018, pp. 603–8. Accessed 2 June 2025.“Table 2.”
[27] Dadi, Ghita, et al. “Persistent Depersonalization/Derealization Disorder Induced by Synthetic Cannabinoids.” American Journal of Psychiatry, vol. 173, no. 8, Aug. 2016, pp. 839–40. Accessed 2 June 2025.“The patient asked for help nearly 6 months later, noting continuing unrest even though he immediately stopped using K2 and cannabis, ... He described a detachment from his own thoughts, body, and feelings and his impression ‘of not being there.’ ... He received fluoxetine treatment for 6 months without any improvement. The symptoms remained persistent for more than 17 months.”
[28] van de Giessen, E., et al. “Deficits in Striatal Dopamine Release in Cannabis Dependence.” Molecular Psychiatry, vol. 22, no. 1, Jan. 2017, pp. 68–75. Accessed 2 June 2025.“Table 2.”
[29] KESHAVAN, M. S., and W. A. LISHMAN. “Prolonged Depersonalization Following Cannabis Abuse.” Addiction, vol. 81, no. 1, Jan. 1986, pp. 140–42. Accessed 2 June 2025.“A feeling as if his ‘brain had dissociated from his mind’. These had lasted about 6 months. He had been smoking ‘Ganja’ heavily and regularly for about one year previously, ... A 20-year-old unemployed man was referred for advice on account of persistent feelings of unreality lasting for some 10 months, ...He had left school at the age of 16 and since then had been smoking marihuana regularly.”
[30] Hotham, James, et al. “Association of Cannabis, Cannabidiol and Synthetic Cannabinoid Use with Mental Health in UK Adolescents.” British Journal of Psychiatry, vol. 223, no. 4, July 2023. Accessed 2 June 2025.“Table 2.”
[31] Hancox, Jules C., et al. “Synthetic Cannabinoids and Potential Cardiac Arrhythmia Risk: An Important Message for Drug Users.” Therapeutic Advances in Drug Safety, vol. 11, Jan. 2020, pp. 1–4. Accessed 2 June 2025.“However, there is a reported 30-fold odds (a per event risk of 0.0006017) of requiring emergency medical treatment following SCRA use over those who use cannabis alone (a per event risk of 0.0000201)”
[32] Cohen, Koby, et al. “Chronic Use of Synthetic Cannabinoids Is Associated with Impairment in Working Memory and Mental Flexibility.” Frontiers in Psychiatry, vol. 11, June 2020. Accessed 3 June 2025.“Table 2 –3.”
[33] Guler, EM, et al. “Investigation of DNA Damage, Oxidative Stress, and Inflammation in Synthetic Cannabinoid Users.” Human & Experimental Toxicology, vol. 39, no. 11, SAGE Publishing, June 2020, pp. 1454–62. Accessed 3 June 2025.“Table 1.”
[34] Sherpa, Dolkar, et al. “Synthetic Cannabinoids: The Multi-Organ Failure and Metabolic Derangements Associated with Getting High.” Journal of Community Hospital Internal Medicine Perspectives, vol. 5, no. 4, Jan. 2015, p. 27540. Accessed 3 June 2025.“Initial vital signs showed normal blood pressure (125/81 mmHg), tachycardia (158 beats/min), tachypnea (30/min), high grade temperature (106.58F), ..., he had been smoking cannabinoids regularly for 15 years and had recently started using K2 via a bong device twice daily 3 weeks prior to presentation.”
[35] Rodriguez de Fonseca, F. “Activation of Corticotropin-Releasing Factor in the Limbic System during Cannabinoid Withdrawal.” Science, vol. 276, no. 5321, June 1997, pp. 2050–54. Accessed 3 June 2025.“Table 1.”
[36] Winstock, Adam, et al. “Risk of Emergency Medical Treatment Following Consumption of Cannabis or Synthetic Cannabinoids in a Large Global Sample.” Journal of Psychopharmacology, vol. 29, no. 6, June 2015, pp. 698–703. Accessed 3 June 2025.“The most commonly reported symptoms amongst both cannabis and SC EMT seekers were panic, anxiety and paranoia, ... a higher proportion of SC EMT seekers (28.6%) reported a recovery time of two weeks.”
[37] Samaan, John, et al. “Synthetic Cannabis Overdose and Withdrawal in a Young Adult: A Case Report, Commentary on Regulation, and Review of the Literature.” Case Reports in Psychiatry, vol. 1, Sept. 2016, pp. 1–7. Accessed 3 June 2025.“The patient mentioned that the symptoms subsided several weeks (2-3 weeks) after his discharge from the hospital, ... symptoms of panic attacks, including palpitations, shortness of breath, diaphoresis, chest tightness, and hand numbness.”
[38] Thakur, Tanu, and Vikas Gupta. “Auditory Hallucinations.” PubMed, StatPearls Publishing, 13 Feb. 2023. Accessed 4 June 2025.“The prevalence of auditory hallucinations in the general population ranges from 5% to 28%. Auditory hallucinations are most prevalent in patients who have psychosis. They are observed in 75% of individuals with schizophrenia.”

About the author

Mischa Ezekpo

Mischa Ezekpo has a Bachelors degree in Psychology from Northumbria
University, and a Masters degree in Childhood Development and
Wellbeing, from Manchester Metropolitan University. Since 2018, Mischa
has written and published work on Addiction, Mental Health, Depression, and Eating Disorders. Content reviewed by Laura Morris (Clinical Lead).

Share 0

Last Updated: February 4, 2026