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1. The cannabis withdrawal syndrome: current insights

Author

Bonnet U and Preuss UW

Subjects
marijuana, cannabis, withdrawal syndrome, humans, treatment, course, Public aspects of medicine, RA1-1270
Abstract

Udo Bonnet,1,2 Ulrich W Preuss3,4 1Department of Psychiatry, Psychotherapy and Psychosomatic Medicine, Evangelisches Krankenhaus Castrop-Rauxel, Academic Teaching Hospital of the University of Duisburg-Essen, Castrop-Rauxel, 2Department of Psychiatry and Psychotherapy, Faculty of Medicine, LVR-Hospital Essen, University of Duisburg-Essen, Essen, 3Vitos-Klinik Psychiatrie und Psychotherapie Herborn, Herborn, 4Martin Luther University Halle-Wittenberg, Halle (Saale), Germany Abstract: The cannabis withdrawal syndrome (CWS) is a criterion of cannabis use disorders (CUDs) (Diagnostic and Statistical Manual of Mental Disorders – Fifth Edition) and cannabis dependence (International Classification of Diseases [ICD]-10). Several lines of evidence from animal and human studies indicate that cessation from long-term and regular cannabis use precipitates a specific withdrawal syndrome with mainly mood and behavioral symptoms of light to moderate intensity, which can usually be treated in an outpatient setting. Regular cannabis intake is related to a desensitization and downregulation of human brain cannabinoid 1 (CB1) receptors. This starts to reverse within the first 2 days of abstinence and the receptors return to normal functioning within 4 weeks of abstinence, which could constitute a neurobiological time frame for the duration of CWS, not taking into account cellular and synaptic long-term neuroplasticity elicited by long-term cannabis use before cessation, for example, being possibly responsible for cannabis craving. The CWS severity is dependent on the amount of cannabis used pre-cessation, gender, and heritable and several environmental factors. Therefore, naturalistic severity of CWS highly varies. Women reported a stronger CWS than men including physical symptoms, such as nausea and stomach pain. Comorbidity with mental or somatic disorders, severe CUD, and low social functioning may require an inpatient treatment (preferably qualified detox) and post-acute rehabilitation. There are promising results with gabapentin and delta-9-tetrahydrocannabinol analogs in the treatment of CWS. Mirtazapine can be beneficial to treat CWS insomnia. According to small studies, venlafaxine can worsen the CWS, whereas other antidepressants, atomoxetine, lithium, buspirone, and divalproex had no relevant effect. Certainly, further research is required with respect to the impact of the CWS treatment setting on long-term CUD prognosis and with respect to psychopharmacological or behavioral approaches, such as aerobic exercise therapy or psychoeducation, in the treatment of CWS. The up-to-date ICD-11 Beta Draft is recommended to be expanded by physical CWS symptoms, the specification of CWS intensity and duration as well as gender effects. Keywords: marijuana, humans, neurobiology, treatment, course, detoxification, symptoms

Published
2017

3. Phenibutanan Illegal Food Supplement With Psychotropic Effects and Health Risks.

Author

Bonnet, U., Scherbaum, N., Schaper, A., and Soyka, M.

Abstract

Background: Phenibut (β-phenyl-γ-aminobutyric acid) is an analog of the neurotransmitter gamma-aminobutyric acid (GABA). Like abapentin and pregabalin, it inhibits α2-δsubunits of voltage-dependent presynaptic calcium channels. The potential harm resulting from the use of these gabapentinoids is currently a matter of debate. Methods: This review is based on pertinent publications retrieved by a selective literature search and on cases reported to the Giftinformationszentrum-Nord (GIZ-Nord), a poison information center at the University of Gttingen, Germany. Results: Phenibut is a prescription drug in Russia but its production, possession, use, trafficking, or administration is illegal in Germany. The phenibut toxicity syndrome resembles that of gabapentinoids and GABA mimetics: benzodiazepine-like withdrawal symptoms including epileptic seizures, delirium and paradoxical activation have been described, as have cases of abuse and dependence. A few cases of use in the setting of multidrug abuse, and of phenibut-related death, have been described to date in the USA. The GIZ-Nord received 17 inquiries about phenibut, 55 about gabapentin, and 126 about pregabalin over the period 20082022. Over the same period, the GIZ-Nord was informed of 1207 cases involving Z substances and 4324 involving benzodiazepines. In the majority of the registered intoxications, including those with phenibut, the symptoms were mild. Overdoses of phenibut (2100 g) were reported in 15 of the 17 cases; 8 of the persons who had taken an overdose were somnolent. In such cases, observation in intensive care was recommended. Respiratory depression or coma was not encountered in any case, not even in the patient who had taken 100 g of phenibut. Conclusion: Phenibut causes symptoms resembling those of gabapentinoid and benzodiazepine use. There have been reports of phenibut use in combination with other psychotropic drugs; in particular, its use together with opiates could increase the risk of coma and respiratory depression. No deaths due to phenibut intoxication have been published in Germany or elsewhere in Western Europe, although such cases may have been overlooked, as this drug is still largely unknown to Western medicine. [ABSTRACT FROM AUTHOR]

Published
2024
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9. List of Contributors

Author

Aas, M., primary, Abalo, R., additional, Abdel-Salam, O.M.E., additional, Abilio, V.C., additional, Adelli, G.R., additional, Ahmed, M.H., additional, Alhouayek, M., additional, Allen, J., additional, Allsop, D.J., additional, Almada, R.C., additional, Almeida, V., additional, Aloway, A., additional, Amanullah, S., additional, Ames, S.L., additional, Annaheim, B., additional, Appendino, G., additional, Aramaki, H., additional, Arias-Horcajadas, F., additional, Ariza, C., additional, Arnold, J.C., additional, Asmaro, D., additional, Auwärter, V., additional, Bachmann, S., additional, Baker, A., additional, Balter, R.E., additional, Baraldi, P.G., additional, Barber, P.A., additional, Barbería, E., additional, Bar-Sela, G., additional, Bastiani, L., additional, Basu, D., additional, Basurte, I., additional, Beck, O., additional, Behrendt, S., additional, Bergen-Cico, D., additional, Berrendero, F., additional, Bhagav, P., additional, Bhattacharyya, S., additional, Bioque, M., additional, Bolkent, S., additional, Boman, J.H., additional, Bondallaz, P., additional, Bonnet, U., additional, Borges, R.S., additional, Borowiak, K., additional, Boschi, I., additional, Brents, L.K., additional, Bridts, C.H., additional, Bruno, A., additional, Burrows, B.T., additional, Busatto, G.F., additional, Callaghan, R.C., additional, Campos, A.C., additional, Camsari, U.M., additional, Canfield, A., additional, Carra, E., additional, Carrillo-Salinas, F.-J., additional, Cascini, F., additional, Castelli, M.P., additional, Cawich, S.O., additional, Cawston, E.E., additional, Cedro, C., additional, Chagas, M.H.N., additional, Chen, C., additional, Chisari, C., additional, Chtioui, H., additional, Cico, R.D., additional, Ciechomska, I.A., additional, Coimbra, N.C., additional, Cole, J., additional, Cookey, J., additional, Copeland, J., additional, Coskun, Z.M., additional, Crano, W.D., additional, Crippa, J.A.S., additional, Crocker, C.E., additional, Cuesta, M.J., additional, Cunha, P.J., additional, Cutando, L., additional, da Silva, A.B.F., additional, da Silva, J.A., additional, da Silva, V.K., additional, Dan, D., additional, De Boni, R.B., additional, Rodríguez de Fonseca, F., additional, Gómez de Heras, R., additional, de Oliveira, A.C.P., additional, de Souza Crippa, A.C., additional, de Souza Crippa, J.A., additional, Degenhardt, F., additional, Degenhardt, L., additional, Deiana, S., additional, Deonarine, U., additional, Di Forti, M., additional, dos Anjos-Garcia, T., additional, Guimarães dos Santos, R., additional, Drozd, M., additional, Duran, F.L.S., additional, Earleywine, M., additional, Ebo, D.G., additional, Egashira, N., additional, Egnatios, J., additional, Ellert-Miklaszewska, A., additional, ElShebiney, S.A., additional, ElSohly, M.A., additional, Evren, C., additional, Fañanás, L., additional, Faber, M.M., additional, Farag, S., additional, Farré, A., additional, Farré, M., additional, Fatjó-Vilas, M., additional, Favrat, B., additional, Feingold, D., additional, Feliú, A., additional, Fernández, A.A., additional, Fernández-Artamendi, S., additional, Ferrari, A.J., additional, Ferraro, L., additional, Fichna, J., additional, Finlay, D.B., additional, Fiz, J., additional, Flores, Á., additional, Fogel, J.S., additional, Fornari, E., additional, Fortunato, L., additional, Fyfe, T., additional, Gaafar, A.E.D.M., additional, Gade, S., additional, Gaffal, E., additional, Galal, A.F., additional, Gandhi, R., additional, Gates, P., additional, Gatley, J.M., additional, Giroud, C., additional, Glass, M., additional, Goldberg, S.R., additional, González-Ortega, I., additional, González-Pinto, A., additional, Guaza, C., additional, Guillon, V., additional, Guimarães, F.S., additional, Gul, W., additional, Guven, F.M., additional, Hall, W.D., additional, Hallak, J.E.C., additional, Hamerle, M., additional, Haney, M., additional, Harding, H.E., additional, Hassan, S., additional, Haugland, K., additional, Healey, A., additional, Heck, C., additional, Helander, A., additional, Hernandez-Folgado, L., additional, Herzig, D.A., additional, Hesse, M., additional, Hill, M.G., additional, Hirst, R., additional, Hjorthøj, C.R., additional, Hoch, E., additional, Holder, M.D., additional, Holtkamp, M., additional, Hunter, M.R., additional, Ikeda, E., additional, Izumi, Y., additional, Janus, T., additional, Kaminska, B., additional, Kanaan, A.S., additional, Karinen, R., additional, Karl, T., additional, Katsu, T., additional, Kay-Lambkin, F., additional, Kayser, O., additional, Kells, M., additional, Kelly, B.C., additional, Kelly, T.H., additional, Kokona, A., additional, Kumar, A., additional, Kumar, P., additional, La Barbera, D., additional, Lagerberg, T.V., additional, Lahat, A., additional, Larsen, H.J., additional, Laun, A.S., additional, Lecomte, T., additional, Legleye, S., additional, Lev-Ran, S., additional, Lile, J.A., additional, Limberger, R.P., additional, Linares, I.M.P., additional, Lisdahl, K.M., additional, Little, M., additional, Liu, W., additional, Loflin, M.J., additional, Lorente-Omeñaca, R., additional, Lorenzetti, V., additional, Lu, D., additional, Mørland, J., additional, Müller-Vahl, K.R., additional, Machoy-Mokrzyńska, A., additional, Maeder, P., additional, Majumdar, S., additional, Maldonado, R., additional, Maple, K.E., additional, Marrón, T., additional, Martínez-Cengotitabengoa, M., additional, Martín-Fontelles, M. Isabel, additional, Martín-Santos, R., additional, Masuda, K., additional, McRae-Clark, A.L., additional, Mecha, M., additional, Medallo, J., additional, Melle, I., additional, Menahem, S., additional, Mendes-Gomes, J., additional, Mesías, B., additional, Miller, S., additional, Mizrahi, R., additional, Molinaro, S., additional, Moore, C., additional, Moraes, M.F., additional, Moreira, F.A., additional, Moreno-Izco, L., additional, Morris, H.A., additional, Muñoz, E., additional, Muccioli, G.G., additional, Muscatello, M.R.A., additional, Nada, S.A., additional, Naraynsingh, V., additional, Narimatsu, S., additional, Nogueira-Filho, G., additional, Nordentoft, M., additional, Oguz, G., additional, Øiestad, Å.M.L., additional, Øiestad, E.L., additional, Okazaki, H., additional, Olive, M.F., additional, Orio, L., additional, Ozaita, A., additional, Pérez, A., additional, Panagis, G., additional, Pandolfo, G., additional, Panlilio, L.V., additional, Paquin, K., additional, Parakh, P., additional, Parker, L.A., additional, Patel, V.B., additional, Pawson, M., additional, Peres, F.F., additional, Petras, H., additional, Pollastro, F., additional, Porcu, A., additional, Potente, R., additional, Potter, D.E., additional, Potvin, S., additional, Prats, C., additional, Preedy, V.R., additional, Rajendram, R., additional, Rathke, L., additional, Reed, K.L., additional, Repka, M.A., additional, Rigter, H., additional, Rock, E.M., additional, Rohrbacher, H., additional, Rosa, P.G.P., additional, Sánchez-Martínez, F., additional, Sánchez-Torres, A.M., additional, Sałaga, M., additional, Sabato, V., additional, Sanders, A.N., additional, Santos, L.C., additional, Scalese, M., additional, Schaufelberger, M.S., additional, Schröder, N., additional, Scimeca, G., additional, Secades-Villa, R., additional, Selvarajah, D., additional, Senormanci, O., additional, Shivakumar, K., additional, Shrier, L.A., additional, Siciliano, V., additional, Sideli, L., additional, Siegel, J.T., additional, Sleem, A.A., additional, Sobczyński, J., additional, Sodos, L., additional, Solowij, N., additional, Song, Z.-H., additional, Stacy, A.W., additional, Stehle, F., additional, Stogner, J.M., additional, Sussman, S., additional, Swift, W., additional, Szerman, N., additional, Tüting, T., additional, Aghazadeh Tabrizi, M., additional, Taglialatela-Scafati, O., additional, Takahashi, R.N., additional, Takeda, S., additional, Tarricone, I., additional, Tashkin, D.P., additional, Tellioğlu, T., additional, Tellioğlu, Z., additional, Tesfaye, S., additional, Thornton, L., additional, Thylstrup, B., additional, Tibbo, P.G., additional, Todd, G., additional, Torrens, M., additional, Tsai, J., additional, Tseng, H.-H., additional, Turner, A., additional, Tuv, S.S., additional, Ullah, F., additional, Van der Linden, T., additional, Van Gasse, A.L., additional, Vega, P., additional, Vera, G., additional, Verdichevski, M., additional, Vieira Sousa, T.R., additional, Vilela, L.R., additional, Vindenes, V., additional, Walsh, Z., additional, Watanabe, K., additional, Watterson, L.R., additional, White, J.M., additional, Wright, N.E., additional, Yücel, M., additional, Yamamoto, I., additional, Yamaori, S., additional, Zalesky, A., additional, Zalman, D., additional, Zhang, J., additional, Zhang, Y., additional, Zoccali, R., additional, Zorumski, C.F., additional, and Zuardi, A.W., additional

Published
2017
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12. Stopping antidepressants: withdrawal symptoms and rebound effects Review and practical recommendations

Author

Bschor, T., Bonnet, U., Pitzer, M., Baethge, C., Lieb, K., Gertz, H. -J., Muller-Oerlinghausen, B., Bschor, T., Bonnet, U., Pitzer, M., Baethge, C., Lieb, K., Gertz, H. -J., and Muller-Oerlinghausen, B.

Abstract

Stopping antidepressants can cause withdrawal (discontinuation) symptoms, the return of the original illness, and rebound. The latter means that the disease will return stronger, faster, or with greater likelihood than if it had not been treated with medication. The Psychiatry Working Group of the Drug Commission of the German Medical Association (Akda) presents the scientific findings and provides practical recommendations for action. Withdrawal symptoms are multiform; unspecific physical symptoms are predominant. Distinguishing them from the recurrence of depressive symptoms can be difficult. Most of them are mild and self-limiting. There is insufficient evidence on the extent and frequency of rebound depression. The rebound risk implies that when establishing the medication, the short-term benefit must be weighed against the possible long-term risk of chronic depression or the possible need for long-term medication. Patients should be informed about the risk of withdrawal both as early as the joint decision-making process about treatment initiation and regularly during the course of treatment. Withdrawal should take place gradually, except in emergency situations, whereby small steps should be taken, especially in the low-dose range.

Published
2022

33. Zur Ergebnisqualität der allgemeinpsychiatrischen offenstationären Krankenhausbehandlung auf der Mesoebene - eine prospektive Studie aus einem urbanen Allgemeinkrankenhaus.

Author

Langrock, C. and Bonnet, U.

Abstract

Background: Inpatient treatment (meso level) in psychiatric hospitals is commonly assumed to be effective. However, there is very little evidence-based data on this issue. Objectives and methods: First evaluation of the outcome quality of an inpatient general psychiatric treatment in a German general hospital using multifaceted quality indicators (symptom severity, wellbeing, self-efficacy, depressive avoidance, patients' satisfaction with the treatment)was carried out. Patients with a wide range of psychiatric diagnoses (ICD-10 F2-F6) were randomly assigned to this naturalistic single-group pre-post study. For ethical and methodological reasons, only adult inpatients treated in open general psychiatric wards were enrolled. Results: The sample (n = 110, 58.2% females) had a mean age of 47.2 (SD 15.9) years. 67 (60.9 %) and 29 (26.4 %) patients had at least one or two additional psychiatric diagnoses, respectively. 84 (76.4 %) and 62 (56.4 %) patients had a minimum of one or two additional somatic diagnoses, respectively. The treatment lasted 38 (SD 36; median 28.5) days. Significant positive treatment effects for all quality indicators were found at regular hospital discharge. The effect sizes varied between Cohen's d = 0.17 - 0.62 ("intention-to-treat" population, n = 110) and d = 0.28 - 0.99 ("completer" population, n = 70). Discussion and conclusion: This study provides direct evidence for the effectiveness of an open inpatient general psychiatric hospital treatment at the meso level. The results, however, are not representative for all German general psychiatric wards because of major differences between hospitals in personnel resources and framework conditions. [ABSTRACT FROM AUTHOR]

Published
2016
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