Cannabinoide: Indikationen

Erstellt am 06 Jun 2017 20:43
Zuletzt geändert: 18 Oct 2020 22:18

Allgemein

ADHS

Angst

CONCLUSIONS:
CBD seems to be a promising drug for the treatment of PD. However, novel clinical trials involving patients with the PD diagnosis are clearly needed to clarify the specific mechanism of action of CBD and the safe and ideal therapeutic doses of this compound.

Appetitlosigkeit

Empfehlung 23:
Cannabispräparate können zur Verbesserung des Appetits bei Patienten mit Tumorkachexie und Geschmacksstörungen erwogen werden.
(C; starker Konsens)
In dieser kanadischen Studie bei CED-Patienten berichteten über 75 % der Patienten über Nebenwirkungen wie Angst, vermehrten Appetit, einen trockenen Mund, Benommenheit und ein High-Gefühl.

Arthritis, Rheuma, Fibromyalgie

CONCLUSION 4-19:
There is moderate evidence that cannabinoids, primarily nabiximols, are an effective treatment to improve short-term sleep outcomes in individuals with sleep disturbance associated with obstructive sleep apnea syndrome, fibromyalgia, chronic pain, and multiple sclerosis.
  • Walitt B, Klose P, Fitzcharles MA, Phillips T, Häuser W. Cannabinoids for fibromyalgia. Cochrane Database Syst Rev. 2016 Jul 18;7:CD011694. doi: 10.1002/14651858.CD011694.pub2.
Dieser Review untersuchte tatsächlich nur Nabilon. (We found no relevant study with herbal cannabis, plant-based cannabinoids or synthetic cannabinoids other than nabilone in fibromyalgia.)
Der Abstract dieses Cochrane-Rewies enthält zur gefundenen Wirksamkeit folgende Bemerkungen:
Third tier (very low quality) evidence indicated greater reduction of pain and limitations of HRQoL compared to placebo in one study … Third tier evidence indicated better effects of nabilone on sleep than amitriptyline (very low quality evidence). … There were no significant differences between the two drugs noted for pain, mood and HRQoL (very low quality evidence).
Weiter fanden die Autoren mehr Nebenwirkungen für Nabilon als für Amitriptylin oder Plazebo, wobei Plazebo zahlenmäßig (1 vs. 0) mehr Nebenwirkungen hatte als Amitriptylin.
Eine Nicht-Wirkung belegt der Cochrane-Review von Walitt et al. nicht (man könnte auch sagen There is no good evidence of a lack of effect); er belegt lediglich keine bessere Wirkung von Nabilon im Vergleich zu Amitriptylin oder Plazebo, was ein Unterschied ist. Daneben zeigt dieser Review auch keine (oder tendenziell schlechtere) Wirkung für Amitriptylin - was allerdings (in diesem Review) nicht die primäre Fragestellung war.
Gerade im Hinblick auf das Fibromyalgie-Syndrom gibt es in der Versorgung eine Tendenz zu Medikalisierung, Über-Medikation und mit Sicherheit eine beachtliche Iatrogenese.

Im Sinne einer medizinisch vernünftigen Versorgung und Schadensbegrenzung sind der (am 31.03.2017 abgelaufenen) AWMF-Leitlinie "Nicht-spezifische, funktionelle und somatoforme Körperbeschwerden" Hinweise zu entnehmen, wonach praktisch alle medikamentösen Therapien der Fibromyalgie sowohl wirkungslos als auch schädlich sind, wenn sie nicht in ein ganzheitliches Therapieprogramm eingebunden werden.
Andere diesbezüglichen aktuelle Leitlinien der AWMF sind trotz "S3"-Klassifikation von unbefriedigender Qualität.
Die aktuelle Fibromyalgie-Leitlinie empfiehlt neben Amitriptylin eine Reihe anderer potentiell stark nebenwirkungsbehafteter (und potentiell auch abhängig machender) Substanzen wie Duloxetin, Pregabalin, mit einem "Evidenzlevel 1" und starkem Konsens als "Off-Label"-Anwendung; Quetiapin mit einem "Evidenzlevel 2a" - und zieht dazu u.a. auch den Cochrane Review " Amitriptyline for neuropathic pain and fibromyalgia in adults" von 2012 heran - der allerdings keine Evidenz für die Wirksamkeit von Amitriptylin fand.
Die Leitlinie zur Langzeitanwendung von Opioiden bei chronischen nichttumorbedingten Schmerzen, Stand: 29.09.2014, gültig bis 01.10.2019, enthält eine direkte Empfehlung zur Verwendung von Tramadol beim Fibromyalgie-Syndrom.
Aus Sicht des Patientenschutzes ist hier zu bedenken, dass das Abhängigkeitspotential von Tramadol nach der Literatur als wesentlich höher einzuschätzen ist als das aller Cannabidiol-Präparate (für reines Cannabidiol sind überhaupt keine Suchteffekte nachgewiesen) überhaupt und auch höher als bei Cannabis-Blüten mit geringem THC-Gehalt.

Autismus-Spektrum Krankheiten

Autoimmunerkrankungen

Herein, using a well-established mouse model of experimental autoimmune myocarditis (EAM) induced by immunization with cardiac myosin emmulsified in adjuvant resulting in T cell-mediated inflammation, cardiomyocyte cell death, fibrosis and myocardial dysfunction, we studied the potential beneficial effects of CBD. … Chronic treatment with CBD largely attenuated the CD3+ and CD4+ T cell-mediated inflammatory response and injury, myocardial fibrosis and cardiac dysfunction in mice. In conclusion, CBD may represent a promising novel treatment for managing autoimmune myocarditis and possibly other autoimmune disorders and organ transplantation.

Chronisch entzündliche Darmerkrankungen

Three studies (93 participants) that assessed cannabis in people with active CD met the inclusion criteria. One ongoing study was also identified.
AUTHORS' CONCLUSIONS: The effects of cannabis and cannabis oil on Crohn's disease are uncertain. Thus no firm conclusions regarding the efficacy and safety of cannabis and cannabis oil in adults with active Crohn's disease can be drawn. The effects of cannabis or cannabis oil in quiescent Crohn's disease have not been investigated. Further studies with larger numbers of participants are required to assess the potential benefits and harms of cannabis in Crohn's disease. Future studies should assess the effects of cannabis in people with active and quiescent Crohn's disease. Different doses of cannabis and delivery modalities should be investigated.
Two RCTs (92 participants) met the inclusion criteria. One study (N = 60) compared 10 weeks of cannabidiol capsules with up to 4.7% D9-tetrahydrocannabinol (THC) with placebo capsules in participants with mild to moderate UC.
Another study (N = 32) compared 8 weeks of therapy with two cannabis cigarettes per day containing 0.5 g of cannabis, corresponding to 23 mg THC/day to placebo cigarettes in participants with UC who did not respond to conventional medical treatment.
AUTHORS' CONCLUSIONS: The effects of cannabis and cannabidiol on UC are uncertain, thus no firm conclusions regarding the efficacy and safety of cannabis or cannabidiol in adults with active UC can be drawn.There is no evidence for cannabis or cannabinoid use for maintenance of remission in UC. Further studies with a larger number of patients are required to assess the effects of cannabis in UC patients with active and quiescent disease. Different doses of cannabis and routes of administration should be investigated. Lastly, follow-up is needed to assess the long term safety outcomes of frequent cannabis use.
Areas covered: Recent data on the effects of Cannabis/cannabinoids in experimental models of IBD and in clinical trials with IBD patients have been reviewed using a PubMed database search. A short background on the endocannabinoid system is also provided. Expert commentary: Cannabinoids could be helpful for certain symptoms of IBD, but there is still a lack of clinical studies to prove efficacy, tolerability and safety of cannabinoid-based medication for IBD patients, leaving medical professionals without evidence and guidelines.
… experimental data suggest that the endocannabinoid system represents a promising target in the treatment of inflammatory bowel diseases, and this assumption is also confirmed by preliminary clinical studies.
Schlussfolgerungen.
Cannabinoide eignen sich möglicherweise zur symptomatischen Therapie von Morbus-Crohn-assoziierten Beschwerden wie Schmerz, Übelkeit und Appetitlosigkeit.

Demenz

A review of several clinical trials was completed: dextromethorphan/quinidine, scyllo-inositol, brexpiprazole, prazosin, cannabinoids, citalopram, escitalopram, pimavanserin, ITI-007, ORM-12741 show promise in treating agitation.

Ein Review, der Hinweise auf Cannabis-Wirksamkeit zur Behandlung der Agitiertheit fand.

Bei älteren Mäusen fand diese Studie Hinweise eine antidementive Wirkung von THC - bei jüngeren Mäusen hingegen wurden die kognitiven Leistungen negativ beeinflusst. Es wird angenommen, dass die Wirkungsweise von THC altersabhängig vollkommen unterschiedlich ausfallen kann.

Bei älteren Mäusen fand diese Studie Hinweise eine antidementive Wirkung von THC - bei jüngeren Mäusen hingegen wurden die kognitiven Leistungen negativ beeinflusst. Es wird angenommen, dass die Wirkungsweise von THC altersabhängig vollkommen unterschiedlich ausfallen kann. Ist natürlich spekulativ, da keineswegs sicher ist, ob die Ergebnisse auf Menschen übertragbar sind.

MAIN RESULTS:
Only one study (Volicer et al.) met the inclusion criteria. The data in the study report were presented in such a way that they could not be extracted for further analysis and there was insufficient quantitative data to validate the results.
AUTHORS' CONCLUSIONS:
This review finds no evidence that cannabinoids are effective in the improvement of disturbed behaviour in dementia or in the treatment of other symptoms of dementia. More randomized double-blind placebo controlled trials are needed to determine whether cannabinoids are clinically effective in the treatment of dementia.

In diesem Cochrane Review wurde tatsächlich nur eine einzige Studie (zu Dronabinol) ausgewertet. Anhand dieser Studie fand man keinen Hinweis auf positive Effekte von Cannabis bei Verhaltensproblemen bei Demenz.

Letters, case studies, and controlled trials from four electronic databases were included. While findings from six studies showed significant benefits from synthetic cannabinoids—dronabinol or nabilone—on agitation and aggression, definitive conclusions were limited by small sample sizes, short trial duration, and lack of placebo control in some of these studies. Given the relevance and findings to date, methodologically rigorous prospective clinical trials are recommended to determine the safety and efficacy of cannabinoids for the treatment of agitation and aggression in dementia and AD.

Eine Übersichtsarbeit, die auch Fallberichte einschloss; nicht nur kontrollierte Studien. Die untersuchten Substanzen waren Dronabinol und Nabilon; leider kein Cannabidiol. Einige (methodisch wengier gute) Studien fanden "signifikante" Nutzenbelege hinsichtlich Agitiertheit und Aggression. Die Autoren der Übersichtsarbeit plädieren für weitere Studien mit methodisch besserem Design, da die Aussagen der gefundenen positiven Studien mit hoher Irrtumswahrscheinlichkeit behaftet sind.

CONCLUSION 4-13
There is limited evidence that cannabinoids are ineffective treatments for improving the symptoms associated with dementia.
Kommentar:
We agree that the evidence is limited due to the small number of patients enrolled, limits in the study design and reporting, and inconsistent effects.

Der Report der National Academies of Sciences 2017 kommt zu dem Schluss, dass die vorhandene Datenlage nicht belastbar ist und keine sicheren Schlussfolgerungen zum Einsatz von Cannabis bei Demenz erlaubt.

No significant change in patients’ Neuropsychiatric Inventory (NPI) score following THC treatment.

Die Autoren fanden keine signifikante Veränderung in dem NPI-Score (Neuropsychiatric Inventory) in der Folge einer THC-Behandlung.

placebo-controlled crossover design, with each treatment period lasting 6 weeks, was used to investigate effects of dronabinol in 15 patients with a diagnosis of probable Alzhemer's disease who were refusing Food. Eleven patients completed both study periods; one patient who died of a heart attack 2 weeks before the end of the study was also included in the analysis. The study was terminated in 3 patients: one developed a grand mal seizure and 2 developed serious intercurrent infections. Body weight of study subjects increased more during the dronabinol treatment than during the placebo periods. Dronabinol treatment decreased severity of disturbed behavior and this effect persisted during the placebo period in patients who received dronabinol first. Adverse reactions observed more commonly during the dronabinol treatment than during placebo periods included euphoria, somnolence and tiredness, but did not require discontinuation of therapy. These results indicate that dronabinol is a promising novel therapeutic agent which may be useful not only for treatment of anorexia but also to improve disturbed behavior in patients with Alzheimer's disease.

Dies war die einzige, in dem Cochrane Review von 2009 eingeschlossene Studie.

CONCLUSIONS:
The study suggests that dronabinol was able to reduce nocturnal motor activity and agitation in severely demented patients. Thus, it appears that dronabinol may be a safe new treatment option for behavioral and circadian disturbances in dementia.

Eine Studie, die zu dem Ergebnis kam, dass Dronabinol die nächtliche motorische Aktivität und Agitiertheit schwer dementer Patienten reduzieren kann.

Retrospective chart Review.
CONCLUSION:
This report represents the largest studied cohort of dementia patients treated with dronabinol to date and confirms earlier reports that dronabinol can serve as an adjunctive treatment for neuropsychiatric symptoms in dementia.

Eine retrospektive Analyse von Klinik-Akten; also kein sehr belastbares Studiendesign. Allerdings handelte es sich um eine vergleichsweise große Patientenzahl, die mit Dronabinol behandelt worden war. Ein positiver Effekt auf neuropsychiatrische bei zusätzlicher Gabe von Dronabinol wurde beschrieben.

Case Report:
A 71 year old dementia patient suffering from sexual disinhibition who was non-responsive to conventional psychiatric intervention was treated with nabilone. The outcome was a subsequent reduction in disinhibition in sexual behavior, thus illuminating a new trait that might be beneficial in patients with dementia.

Ein Fallbericht über einen 71-jährigen Patienten mit vollständiger sexueller Enthemmung trotz konventioneller psychiatrischer Behandlung. Durch Nabilon konnte das über-sexualisierte Verhalten reduziert bzw. normalisiert werden.

Depression

Entzündung

Abstract
A number of studies have implicated cannabinoids as potent anti-inflammatory mediators. However, the exact mechanism by which cannabinoids exert these effects remains to be fully explained. The recent resurgence in interest regarding the metabolic adaptations undergone by activated immune cells has highlighted the intricate connection between metabolism and an inflammatory phenotype. In this regard, evidence suggests that cannabinoids may alter cell metabolism by increasing AMPK activity. In turn, emerging evidence suggests that the activation of AMPK by cannabinoids may mediate an anti-inflammatory effect through a range of processes. First, AMPK may promote oxidative metabolism, which have been shown to play a central role in immune cell polarisation towards a tolerogenic phenotype. AMPK activation may also attenuate anabolic processes which in turn may antagonise immune cell function. Furthermore, AMPK activity promotes the induction of autophagy, which in turn may promote anti-inflammatory effects through various well-described processes. Taken together, these observations implicate cannabinoids to mediate part of their anti-inflammatory effects through alterations in immune cell metabolism and the induction of autophagy.

Epilepsie

RESULTS:
The median frequency of convulsive seizures per month decreased from 12.4 to 5.9 with cannabidiol, as compared with a decrease from 14.9 to 14.1 with placebo (adjusted median difference between the cannabidiol group and the placebo group in change in seizure frequency, -22.8 percentage points; 95% confidence interval [CI], -41.1 to -5.4; P=0.01). The percentage of patients who had at least a 50% reduction in convulsive-seizure frequency was 43% with cannabidiol and 27% with placebo (odds ratio, 2.00; 95% CI, 0.93 to 4.30; P=0.08). The patient's overall condition improved by at least one category on the seven-category Caregiver Global Impression of Change scale in 62% of the cannabidiol group as compared with 34% of the placebo group (P=0.02). The frequency of total seizures of all types was significantly reduced with cannabidiol (P=0.03), but there was no significant reduction in nonconvulsive seizures. The percentage of patients who became seizure-free was 5% with cannabidiol and 0% with placebo (P=0.08). Adverse events that occurred more frequently in the cannabidiol group than in the placebo group included diarrhea, vomiting, fatigue, pyrexia, somnolence, and abnormal results on liver-function tests. There were more withdrawals from the trial in the cannabidiol group.
CONCLUSIONS:
Among patients with the Dravet syndrome, cannabidiol resulted in a greater reduction in convulsive-seizure frequency than placebo and was associated with higher rates of adverse events. (Funded by GW Pharmaceuticals; ClinicalTrials.gov number, NCT02091375).
Kommentare zu dieser Studie:
Tang R, Fang F. Trial of Cannabidiol for Drug-Resistant Seizures in the Dravet Syndrome. N Engl J Med. 2017 Aug 17;377(7):699. doi: 10.1056/NEJMc1708349.
To summarize, in view of the good outcome in a significant number of patients, which is not significantly worse than other accepted options for patients with refractory epilepsy, it seems that medical cannabis should be considered a viable Treatment Option. …
RESULTS:
Four subjects had data through week 14, one of whom initially withdrew for lack of efficacy but because of other benefits re-enrolled with a lower dose. Two subjects at week 14 and three subjects with bilateral brain involvement had at the last visit a greater than 50% seizure reduction, reported an improved quality of life, and remained on cannabidiol 63-80 weeks after starting the drug. Three subjects reported mild side effects considered related to cannabidiol.
CONCLUSION:
This study suggests that cannabidiol may be well tolerated as adjunctive medication for seizure management and provides initial data supporting further study of cannabidiol in individuals with Sturge-Weber syndrome.
RESULTS:
The evaluation examined 15 patients with refractory epilepsies, who received cannabidiol over a period ranging from one month to one year. The frequency of seizures decreased in 40% of the patients, 60% of the patients were seen to have control over 50% of their seizures and in 27% of them the seizures disappeared completely. Neurocognitive changes were also reported: behaviour improved in 73%; 60% reported an improvement in language; in 50% sleep improved; 43% reported improvements in eating habits; and 100% said their mood had improved. The overall perception of the illness was that there had been improvements in 73% of respondents. The most common side effects were drowsiness and fatigue.
Cannabidiol reduced the frequency of convulsive seizures compared with placebo in Dravet syndrome, a childhood epilepsy disorder with a high mortality rate and no approved treatment in the United States, reported a clinical trial in the New England Journal of Medicine.
The study randomly assigned 120 children and young adults with the syndrome and drug-resistant seizures to receive either cannabidiol (20 mg/kg of body weight per day) or placebo, in addition to standard antiepileptic treatment.
RESULTS:
Of 272 combined patients from Washington State and California, 37 (14%) found cannabis ineffective at reducing seizures, 29 (15%) experienced a 1-25% reduction in seizures, 60 (18%) experienced a 26-50% reduction in seizures, 45 (17%) experienced a 51-75% reduction in seizures, 75 (28%) experienced a 76-99% reduction in seizures, and 26 (10%) experienced a complete clinical response. Overall, adverse effects were mild and infrequent, and beneficial side effects such as increased alertness were reported. The majority of patients used cannabidiol (CBD)-enriched artisanal formulas, some with the addition of delta-9-tetrahydrocannabinol (THC) and tetrahydrocannabinolic acid (THCA). Four case reports are included that illustrate clinical responses at doses <0.1mg/kg/day, biphasic dose-response effects, the use of THCA for seizure prevention, the use of THC for seizure rescue, and the synergy of cannabinoids and terpenoids in artisanal preparations.

Glaukom

Glaucoma is often caused by an anomalously high intraocular pressure (IOP) on the eye [261]. This pressure can be controlled, therefore for most treatments the main goal is to decrease it [261].
In 1998, a review performed by Green [262] came into realization that oral or topical cannabinoids administration would be a good option for glaucoma therapy. However, the same did not happen for smoked marijuana. In spite of IOP reduction on smoking marijuana users, its toxic effects surpassed what was supposed to be beneficial. Nonetheless, only THC is mentioned, and the author defended that further investigation regarding cannabinoids should be done.
In 2006, a trial with six participants was conducted by Tomida et al. [263]. Five milligrams of THC was administrated sublingually and had an effect on the reduction of IOP. Contrarily , 40 mg of CBD increased IOP. Overall, studies are promising, regarding sublingual route administration of THC. However, taking into account that TCH mechanisms on reducing IOP is not yet fully understood, further research and studies need to be performed.
A recent study by Miller and colleagues [264] tested two phytocannabinoids on mice. THC and CBD were applied atopically. Results showed that 5 mM of THC reduced IOP at a rate of 30% for at least 8 h. The mechanism is associated with cannabinoid-related receptors (CB1 and GPR18). Diversely, CBD was counterproductive, because it diminished THC effects, which was the opposite desire outcome [264].
Regardless of the few and redundant studies on this topic, it is possible to conclude that topical and oral administration of cannabinoids have a potential to become part of anti-glaucoma treatment, encouraging research to pursue such an agenda in the field.

"Diese Studie wirft wichtige Fragen bezüglich der Beziehung zwischen den Hauptbestandteilen von Cannabis und ihrer Wirkung auf das Auge auf. Dies legt auch die Notwendigkeit nahe, mehr über die möglichen unerwünschten Nebenwirkungen von CBD zu erfahren. Insbesondere aufgrund seiner Verwendung bei Kindern…"
"Vor über 45 Jahren gab es Studien, in denen Beweise dafür gefunden wurden, dass THC den Druck im Auge senkt, aber bis zu dieser Studie hat niemand die spezifischen Neurorezeptoren identifiziert, die an dem Prozess beteiligt sind. Diese Ergebnisse könnten wichtige Auswirkungen auf die zukünftige Forschung zur Verwendung von Cannabis als Therapie des Augeninnendrucks haben", führte Straiker abschließend aus.
Zitiert nach Alexandra Latour auf Leafly: Glaukom: CBD erhöht Augendruck

"Nach Forschung an der Universität Aachen aus dem Jahr 2007 reduzierte eine orale Einzeldosis von 7,5 mg THC, die acht gesunden Ärzten in einem Selbstversuch verabreicht worden war, den Augeninnendruck und verbesserte darüber hinaus die Durchblutung der Netzhaut. Die Werte waren vor und zwei Stunden nach der THC-Gabe gemessen worden. THC führte zu einer signifikanten mittleren Reduzierung des Augeninnendrucks von 13,2 mm Hg auf 11,8 mm Hg."

An Italian law approved in 201519 authorizes the use of cannabis to treat chronic pain. The law allows for the utilization of cannabis not only for neuropathic pain but also for all chronic pain conditions, as well as for spasticity, cachexia, and anorexia among AIDS and cancer patients, ocular hypertension in glaucoma, the alleviation of spasms in Tourette syndrome, and some types of epilepsy, reiterating that cannabis-based drugs should be prescribed only "when other available medications have proven to be ineffective or inadequate to the therapeutic needs of the patient."

Glaucoma causes damage to the optic nerve and compromises the visual field. The main risk factor of the disease is the level of the intra-ocular pressure. Therapeutic options include medical and surgical treatment, aimed to lower the intra-ocular pressure. Consumption of the cannabis plant (Cannabis Satival has been known since ancient times. It can be consumed orally, topically, intra-venous or by inhalation. The main active ingredient of cannabis is THC (Tetra-Hydro-Cannabinol). One of THC's reported effects is the reduction of intra-ocular pressure. Several studies have demonstrated temporary intra-ocular pressure decrease in both healthy subjects and glaucoma patients following topical application or systemic consumption. The effect was a short term one. It was followed by the development of resistance to the drug after prolonged intake and it was also accompanied by topical and systemic side effects. Cannabis may be considered as a therapeutic option in glaucoma. Its limited effect, development of resistance, acquired side effects and the accompanying psycho-active influence limit its advantage and cause its efficacy to be dubious. Therefore, cannabis treatment for glaucoma currently seems impractical and is not recommended by either the Israeli or the American glaucoma societies.

Topical application of 2% THC ophthalmic solution resulted in moderate reduction of mean IOP in clinically normal dogs. Further research is needed to determine efficacy in dogs with glaucoma.

PATIENTS AND METHODS:
A randomized, double-masked, placebo-controlled, 4 way crossover study was conducted at a single center, using cannabis-based medicinal extract of Delta-9-THC and CBD. Six patients with ocular hypertension or early primary open angle glaucoma received a single sublingual dose at 8 AM of 5 mg Delta-9-THC, 20 mg CBD, 40 mg CBD, or placebo. Main outcome measure was IOP. Secondary outcomes included visual acuity, vital signs, and psychotropic effects.
RESULTS:
Two hours after sublingual administration of 5 mg Delta-9-THC, the IOP was significantly lower than after placebo (23.5 mm Hg vs. 27.3 mm Hg, P=0.026). The IOP returned to baseline level after the 4-hour IOP measurement. CBD administration did not reduce the IOP at any time. However, the higher dose of CBD (40 mg) produced a transient elevation of IOP at 4 hours after administration, from 23.2 to 25.9 mm Hg (P=0.028). Vital signs and visual acuity were not significantly changed. One patient experienced a transient and mild paniclike reaction after Delta-9-THC administration.
CONCLUSIONS:
A single 5 mg sublingual dose of Delta-9-THC reduced the IOP temporarily and was well tolerated by most patients. Sublingual administration of 20 mg CBD did not reduce IOP, whereas 40 mg CBD produced a transient increase IOP rise.

Geriatrische Patienten

Kinder und Jugendliche

Kognition

Multiple Sklerose

Neurose, Tic, Tourette

  • Grant JE, Odlaug BL, Chamberlain SR, Kim SW. Dronabinol, a cannabinoid agonist, reduces hair pulling in trichotillomania: a pilot study. Psychopharmacology (Berl) 2011;218(3):493-502.

  • Jakubovski E, Müller-Vahl K. Speechlessness in Gilles de la Tourette Syndrome: Cannabis-Based Medicines Improve Severe Vocal Blocking Tics in Two Patients. Int J Mol Sci. 2017,18,1739; doi:10.3390/ijms18081739.
  • Trainer D, Evans L, Bird R. Severe motor and vocal tics controlled with Sativex. Ausualasien Psychiatry 2016, Vol 24(6)541-544. DOI:101177/1039856216663737.
  • Szejko, N, Jakubovski E, Müller-Vahl K. Possible Role of the Endocannabinoid System in Tourette Syndrome. Buchkapitel.
  • Müller-Vahl KR, Prevedel H, Theloe K, Kolbe H, Emrich HM, Schneider U. Treatment of tourette Syndrome with delta-9-telrahydrocannabinol (A9-THC): No influence on neuropsychological Performance. Neuropsychopharmacology. 2n03;28(2):384-388.
  • Müller-Vahl KR, Schneider U, Prevedel H, Theloe K, Kolbe H, Daldrup T, et al. 9-tetrahydrocannabinol (THC) is effective in the treatment of tics in Tourette Syndrome: A 6-week randomized trial. The Journal of Clinical Psychiatry. 2003;64(4):459-465.
  • Müller-Vahl KR, Schneider U, Koblenz A, Jöbges M, Kolbe EI, Daldrup T, et al. Treatment of Tourette's Syndrome with Delta 9-tetrahydrocannabinol (THC): A randomized crossover Trial. Pharmacopsychiatry. 2002;35(2);57-61.
  • Müller-Vahl K. Combined treatment of Tourette Syndrome with 9-THC and dopamine receptor antagonists. Journal of Cannabis Theraphy. 2002;2:145-154.
  • Müller-Vahl K, Schneider U, Kolbe H, Emrich HM. Treatment of Tourette's Syndrome with delta-9-tetrahydrocannabinoi [3], Am J Psych 1999;156:495.
  • Müller-Vahl KRK. Cannabinoids: Possible role in patho-physiology and therapy of Gilles de la Tourette Syndrome. Acta Psychiatrica Scandinavica 1998;98:502-506.

Obstruktive Schlafapnoe

Onkologie

Results: In a multivariate model, cannabis was the only significant factor that reduced RR to immunotherapy (37.5% RR in nivolumab alone compared with 15.9% in the nivolumab-cannabis group (p = .016, odds ratio = 3.13, 95% confidence interval 1.24-8.1). Cannabis use was not a significant factor for PFS or OS. Factors affecting PFS and OS were smoking (adjusted hazard ratio [HR] = 2.41 and 2.41, respectively (and brain metastases (adjusted HR = 2.04 and 2.83, respectively).

Conclusions: Despite various limitations, this preliminary study demonstrated a weight increase of ≥10% in 3/17 (17.6%) patients with doses of 5mgx1 or 5mgx2 capsules daily, without significant side effects. The results justify a larger study with dosage-controlled cannabis capsules in CACS.
Studie der Firma CannabiCs: CannabiCs Clinical Trials: Cannabics has successfully conceptualized, funded, executed and concluded two clinical trials, Cannabics SR 5mg for Cancer Anorexia Cachexia Syndrome – CACS, and for the Screening of Potential Anticancer Cannabinoid Compounds. (NCT02359123)

While there is a developing understanding of potential mechanisms of action, with the extracellular signal-regulated kinase pathway emerging as a critical signaling juncture in combination with an important role for ceramide and lipid signaling, the relative importance of each pathway is yet to be determined. The interplay between the intracellular pathways of autophagy versus apoptosis is a recent development that is discussed. Overall, there is still a great deal of conflicting evidence around the future utility of the cannabinoids, natural or synthetic, as therapeutic agents.
CONCLUSIONS:
These results demonstrate that the role of endocannabinoids for urological malignancies is an area of active research. Further research is required not only to evaluate the crosstalk between cancer signaling pathways and cannabinoids, but also large randomized clinical studies with urological patients need to be conducted before cannabinoids can be introduced as potential therapeutic options for urological neoplasms.

Therapieassoziierte Übelkeit

RESULTS/CONCLUSIONS:
Nabilone is superior to placebo, domperidone and prochlorperazine but not metoclopramide or chlorpromazine. Cannabinoids do not add to benefits of 5-HT(3) receptor antagonists. Side effects are greater for nabilone than for prochlorperazine, in most studies patients prefered nabilone over prochlorperazine. Nabilone is ineffective in acute pain but benefits in neuropathic pain and central hypersensitization. Recent guidelines place nabilone as a second to fourth line drug for neuropathic pain.
CONCLUSION 4-3:
There is conclusive evidence that oral cannabinoids are effective antiemetics in the treatment of chemotherapy-induced nausea and vomiting.
Cannabinoids are probably effective but produce frequent side effects.
AUTHORS' CONCLUSIONS:
Cannabis-based medications may be useful for treating refractory chemotherapy-induced nausea and vomiting. However, methodological limitations of the trials limit our conclusions and further research reflecting current chemotherapy regimens and newer anti-emetic drugs is likely to modify these conclusions.
CONCLUSIONS:
With safe and effective antiemetics available, CBs cannot be recommended as first- or second-line therapy for CINV. Some guidelines recommend pharmaceutical CBs as third-line treatment in the management of breakthrough nausea and vomiting. Due to the lack of RCT data and safety concerns, herbal cannabis cannot be recommended for CINV.
CONCLUSIONS:
In selected patients, the cannabinoids tested in these trials may be useful as mood enhancing adjuvants for controlling chemotherapy related sickness. Potentially serious adverse effects, even when taken short term orally or intramuscularly, are likely to limit their widespread use.

Tumorschmerzen

CONCLUSION:
This study showed that the long-term use of THC/CBD spray was generally well tolerated, with no evidence of a loss of effect for the relief of cancer-related pain with long-term use. Furthermore, patients who kept using the study medication did not seek to increase their dose of this or other pain-relieving medication over time, suggesting that the adjuvant use of cannabinoids in cancer-related pain could provide useful benefit.

Palliativversorgung

Bei Patienten mit Tumorschmerzen, die nicht ausreichend auf eine Opioidtherapie ansprechen, kann ein Therapieversuch über einige Tage mit Dosistitration indiziert sein (individueller Heilversuch). Wenn dadurch ausreichende Schmerzlinderung erzielt wird, sollte die Therapie fortgesetzt werden.
Ein individueller Heilversuch („off label“) mit Cannabinoiden bei Tumorschmerzen und bei HIV-bedingter Kachexie kann indiziert sein und sollte von den Kostenträgern finanziert werden.
Cannabinoide führen bei Patienten mit HIV-bedingter Kachexie zu einer Appetitsteigerung, allerdings ist die Therapie mit Megestrol effektiver.
NB: Megestrol ist in Deutschland für keine Patientengruppe zur Appetitsteigerung zugelassen.

Pankreatitis, chronisch

(de Vries M, van Rijckevorsel DC, Vissers KC, et al.; Pain and Nociception Neuroscience Research Group. Tetrahydrocannabinol Does Not Reduce Pain in Patients With Chronic Abdominal Pain in a Phase 2 Placebo-controlled Study. Clin Gastroenterol Hepatol. 2016 Oct 5. pii: S1542-3565(16)30858-8.

Es handelt sich NICHT um eine Studie bei Patienten mit chronischer Pankreatitis!

Nebenwirkungen : Es gab in dieser Phase-2-Studie 7 Teilnehmer der THC-Gruppe, die aufgrund von Nebenwirkungen die Studie beendeten gegenüber nur 2 in der Plazebo-Gruppe. Der Text enthält die Information, dass alle Nebenwirkungen milder bis moderater Natur waren – darüber hinaus wurden auch in der Placebo-Gruppe außergewöhnlich viele Nebenwirkungen berichtet. Die Studienautoren diskutieren einen Nocebo-Effekt.)

Parkinson-Syndrom, Parkinson-Krankheit

We found four randomized controlled trials (RCTs) involving the administration of agonists/antagonists of the cannabinoid 1 receptor, showing that these compounds were well tolerated, but only one study found positive results (reductions on levodopa-induced dyskinesia). We found seven preclinical models of PD using CBD, with six studies showing a neuroprotective effect of CBD. We found three trials involving CBD and PD: an open-label study, a case series, and an RCT. CBD was well tolerated, and all three studies reported significant therapeutic effects in non-motor symptoms (psychosis, rapid eye movement sleep behaviour disorder, daily activities, and stigma). However, sample sizes were small and CBD treatment was short (up to 6 weeks). Large-scale RCTs are needed to try to replicate these results and to assess the long-term safety of CBD.
Übersetzt
Wir fanden vier randomisierte kontrollierte Studien (RCTs) mit der Gabe von Agonisten/Antagonisten des Cannabinoid-1-Rezeptors, die zeigten, dass diese Substanzen gut vertragen wurden, aber nur eine Studie fand positive Ergebnisse (Verminderung der Levodopa-induzierten Dyskinesie). Wir fanden sieben präklinische Modelle von Morbus Parkinson mit CBD, wobei sechs Studien eine neuroprotektive Wirkung des CBD zeigten. Wir fanden drei Studien mit CBD und Parkinson: eine Open-Label-Studie, eine Fallserie und ein RCT. CBD wurde gut vertragen, und alle drei Studien berichteten über signifikante therapeutische Effekte bei nicht-motorischen Symptomen (Psychose, Störung des Schlafverhaltens bei schnellen Augenbewegungen, tägliche Aktivitäten und Stigma). Die Stichprobengrößen waren jedoch klein, und die Behandlung der CBD war kurz (bis zu 6 Wochen). Um diese Ergebnisse zu replizieren und die langfristige Sicherheit der CBD zu beurteilen, wären groß angelegte RCTs erforderlich.
CONCLUSIONS:
Our findings point to a possible effect of CBD in improving quality of life measures in PD patients with no psychiatric comorbidities; however, studies with larger samples and specific objectives are required before definitive conclusions can be drawn.

Pharmakologie

Psychiatrische Störungen

allgemeine psychiatrische Effekte

We conducted a review of systematic reviews (SRs) and randomized-controlled trials (RCTs) to analyze efficacy and safety of cannabis-based medication in patients with mental disorders. Five data bases were systematically searched (2006-August 2018); 4 SRs (of 11 RCTs) and 14 RCTs (1629 participants) were included. Diagnoses were: dementia, cannabis and opioid dependence, psychoses/schizophrenia, general social anxiety, posttraumatic stress disorder, anorexia nervosa, attention-deficit hyperactivity disorder, and Tourette`s disorder. Outcome variables were too heterogeneous to conduct a meta-analysis. A narrative synthesis method was applied. The study quality was assessed using the risk-of-bias tool and SIGN-checklists. THC- and CBD-based medicines, given as adjunct to pharmaco- and psychotherapy, were associated with improvements of several symptoms of mental disorders, but not with remission. Side effects occurred, but severe adverse effects were mentioned in single cases only. In order to provide reliable treatment recommendations, more and larger RCTs with follow-up assessments, consistent outcome measures and active comparisons are needed.
Although trials with positive findings were identified for anorexia nervosa, anxiety, PTSD, psychotic symptoms, agitation in Alzheimer's disease and dementia, Huntington's disease, and Tourette syndrome, and dyskinesia in Parkinson's disease, definitive conclusion on its efficacy could not be drawn. Evaluation of these low-quality trials, as rated on the Cochrane risk of bias tools, was challenged by methodological issues such as inadequate description of allocation concealment, blinding and underpowered sample size.
Beneficial effects of cannabidiol (CBD) have been described for a wide range of psychiatric disorders, including anxiety, psychosis, and depression. The mechanisms responsible for these effects, however, are still poorly understood. Similar to clinical antidepressant or atypical antipsychotic drugs, recent findings clearly indicate that CBD, either acutely or repeatedly administered, induces plastic changes. For example, CBD attenuates the decrease in hippocampal neurogenesis and dendrite spines density induced by chronic stress and prevents microglia activation and the decrease in the number of parvalbumin-positive GABA neurons in a pharmacological model of schizophrenia. More recently, it was found that CBD modulates cell fate regulatory pathways such as autophagy and others critical pathways for neuronal survival in neurodegenerative experimental models, suggesting the potential benefit of CBD treatment for psychiatric/cognitive symptoms associated with neurodegeneration. These changes and their possible association with CBD beneficial effects in psychiatric disorders are reviewed here.
RESULTS:
No RCTs have thus far examined the efficacy of marijuana for Tourette's disorder, PTSD, or Alzheimer's disease. Lower-quality studies examined the efficacy of marijuana, Δ⁹-tetrahydrocannabinol, and nabilone; the strength of evidence for the use of cannabinoids for these conditions is very low at the present time. The consequences of chronic cannabinoid exposure includes tolerance, dependence, and withdrawal. Early and persistent marijuana use has been associated with the emergence of psychosis. Marijuana impairs attention, memory, IQ, and driving ability.
CONCLUSIONS:
Given its rapidly changing legal status, there is an urgent need to conduct double-blind, randomized, placebo- or active-controlled studies on the efficacy and safety of marijuana or its constituent cannabinoids for psychiatric conditions. Physicians and policy-makers should take into account the limited existing evidence and balance that with side effects before approving medical marijuana for psychiatric indications.

Posttraumatische Störung

(((((((((("weed"[Tiab] OR "cannabis"[Tiab]) OR "cannabinoid"[Title]) OR "cannabinoids"[Tiab]) OR "thc"[Title] OR "tetrahydrocannabinol"[tiab]) OR "cannabidiol"[Title]) OR "nabilone"[Tiab]) OR "dronabinol"[Tiab]) OR "marinol"[Tiab]) OR "nabiximols"[Tiab]) OR "Marijuana"[Tiab]) AND ("posttraumatic"[Title] OR "ptsd"[Title])

Based on one systematic review, there is evidence from very low-quality studies that smoked marijuana, oral THC, and nabilone are efficacious in treating some symptoms of PTSD, particularly nightmares and sleep quality and quantity. Information regarding adverse events was reported for one observational study included in the systematic review, in which nabilone was discontinued in 28% of participants due to side effects described as mild to moderate (lightheadedness, forgetfulness, dizziness, and headache). Side effects of marijuana and cannabinoids commonly reported in the literature are generally rated as fairly mild, such as dizziness, tiredness, sedation, lightheadedness, headache, anxiety, disorientation, intoxication, nausea, and oromucosal discomfort. More serous reported side effects have been reported, such as seizures, hallucinations, and paranoid reactions. Tolerance, dependence, pulmonary effects, cognitive deficits, and driving impairment are also potential issues.
At least two RCTs are currently planned or underway to evaluate smoked or vapourized marijuana. The first (NCT02517424) will evaluate the safety and efficacy of three different potencies of vaporized marijuana in 42 participants with chronic, treatment-resistant PTSD, and is expected to be completed in April 2018. The other (NCT02759185) will evaluate the safety and efficacy of four different potencies of smoked marijuana in 76 veterans with chronic, treatment-resistant PTSD. Results are expected in October 2018.
Kurzfassung auf deutsch:
Für die posttraumatische Belastungsstörung fand ein HTA-Bericht der renommierten kanadischen Organisation Canadian Agency for Drugs and Technologies in Health (CADTH; Medical Marijuana for Post-Traumatic Stress Disorder: A Review of Clinical Effectiveness and Guidelines) aus dem Jahr 2017 Evidenz aus Studien niedriger Qualität für positive Wirksamkeit.
Studien-Webseite: http://wecanstudy.org/
  • Jetly R, Heber A, Fraser G, Boisvert D. The efficacy of nabilone, a synthetic cannabinoid, in the treatment of PTSD-associated nightmares: A preliminary randomized, double-blind, placebo-controlled cross-over design study. Psychoneuroendocrinology 2015;51:585-8.
  • Roitman P, Mechoulam R, Cooper-Kazaz R, Shalev A. Preliminary, open-label, pilot study of add-on oral Δ9-tetrahydrocannabinol in chronic post-traumatic stress disorder. Clin Drug Investig 2014;34(8):587-91.

Psychose

Design:
In this parallel-group, double-blind, placebo-controlled randomized clinical trial conducted at the South London and Maudsley NHS Foundation Trust in London, United Kingdom, 33 antipsychotic medication-naive participants at clinical high risk (CHR) of psychosis and 19 healthy control participants were studied. Data were collected from July 2013 to October 2016 and analyzed from November 2016 to October 2017.
Intervention:
A total of 16 participants at CHR of psychosis received a single oral dose of 600 mg of CBD, and 17 participants at CHR received a placebo. Control participants were not given any drug. All participants were then studied using functional magnetic resonance imaging (fMRI) while performing a verbal learning task.
Results:
Participants receiving placebo had reduced activation relative to controls in the right caudate during encoding (…) and in the parahippocampal gyrus and midbrain during recall (…). Within these 3 regions, activation in the CBD group was greater than in the placebo group but lower than in the control group (parahippocampal gyrus/midbrain:…); the level of activation in the CBD group was thus intermediate to that in the other 2 groups. There were no significant group differences in task performance.
… Since its discovery, multiple clinical and preclinical studies have linked the endocannabinoid system to schizophrenia. Both the endocannabinoid anandamide and the cannabinoid CB1 receptor are deeply linked to underlying disease processes. Based hereon, clinical trials in schizophrenia have explored cannabidiol, a primary component of Cannabis sativa, and rimonabant, a partial antagonist to the CB1 receptor. …
The relationship between cannabis and psychosis and schizophrenia has tested the field of addiction for decades, and in some ways serves as measure of our ability to provide a credible contribution to public health. As cannabis is used widely, many people are interested in the risks the drug poses to mental health. This paper focuses upon a seminal study examining this, the trajectory of subsequent research findings and what this has meant for understanding and communicating risk factor information. These studies provided evidence of a dose-response relationship between cannabis and psychosis, and that for those individuals with schizophrenia cannabis exacerbated their symptoms. The findings fit with a multi-causal model in which vulnerability interacts with a precipitating agent to produce a disease outcome. Even though this is a common model in epidemiology, it has proved difficult to communicate it in this case. This may be because at a population level the increased risk is weak and the vulnerabilities relatively rare. It may also be because people bring strongly held preconceptions to interpreting a complex multi-causal phenomenon.
Using the principles of “start low, go slow” titration, individuals with little or no experience, histories of bipolar disorder, strong familial schizophrenia, and/or a history of substance abuse begin their process with medical cannabis on a CBD-dominant strain.
Several contraindications have been identified for medical cannabis recommendations. Due in part to the illicit nature of cannabis, research is lacking and there is a significant knowledge gap in this area, and medical cannabis recommendations should always be made with careful consideration of the current health status of the patient.
Psychosis
As previously mentioned, individuals suffering from, or at a high risk of developing, schizophrenia or other psychotic illnesses should only be recommended the use of cannabis under well-monitored conditions. The use of strains with minimal or no THC content is recommended.
Bipolar disorder
Recently, Kim et al found that cannabis use was significantly associated with lower rates of remission of bipolar spectrum patients over a 2-year follow-up period. Studies have also found an association between cannabis misuse and earlier onset of bipolar disorder. Thus, the use of low-THC content strains is recommended for these patients.
RESULTS:
Subjects with a baseline history of heavy cannabis use had a significantly higher risk of death … than those without such a history. The authors found an excess mortality among subjects with psychotic disorders, but the level did not differ between those with a history of cannabis use … and those without such a history … No interaction was observed between cannabis use and diagnosis of psychotic disorders with regard to mortality.
Results show the ability of CBD to counteract psychotic symptoms and cognitive impairment associated with cannabis use as well as with acute THC administration. In addition, CBD may lower the risk for developing psychosis that is related to cannabis use.
Publikation der Studie CBD-CT1; ClinicalTrials.gov. Identifier: NCT00628290.
Im Ergebnis erwies sich Cannabidiol als potentiell vergleichbar effektiv wie Amisulprid, aber besser verträglich. Die Studie war zwar randomisiert und kontrolliert; kann aber nur als explorative Studie gelten, da sie vor dem geplanten Ende aufgrund auslaufender Förderung terminiert werden musste und nicht für alle Patienten (ursprünglich geplant 21 je Gruppe) gemäß Intention-to-treat ausgewertet werden konnte. Der konfirmatorische Nicht-Unterlegenheitstest hatte ein Konfidenzintervall von 0,5-1,59; so dass die Nicht-Unterlegenheit nicht statistisch gesichert werden konnte.
Tetrahydrocannabinol in cannabis can cause symptoms of schizophrenia when acutely administered, and cannabidiol (CBD), another compound in cannabis, can counter many of these effects. CBD may have therapeutic potential for the treatment of psychosis following cannabis use, as well as schizophrenia, possibly with better tolerability than current antipsychotic treatments. CBD may also have anti-inflammatory and neuroprotective properties.
METHOD:
In an exploratory double-blind parallel-group trial, patients with schizophrenia were randomized in a 1:1 ratio to receive CBD (1000 mg/day; N=43) or placebo (N=45) alongside their existing antipsychotic medication.
RESULTS:
After 6 weeks of treatment, compared with the placebo group, the CBD group had lower levels of positive psychotic symptoms (PANSS: treatment difference=-1.4, 95% CI=-2.5, -0.2) and were more likely to have been rated as improved (CGI-I: treatment difference=-0.5, 95% CI=-0.8, -0.1) and as not severely unwell (CGI-S: treatment difference=-0.3, 95% CI=-0.5, 0.0) by the treating clinician.
  • McLoughlin BC, Pushpa-Rajah JA, Gillies D, Rathbone J, Variend H, Kalakouti E, Kyprianou K. Cannabis and schizophrenia. Cochrane Database Syst Rev. 2014 Oct 14;(10):CD004837. doi: 10.1002/14651858.CD004837.pub3.
Cannabinoid as treatment: cannabidiol versus amisulpride - … no data were reported for any of the main outcomes of interest at medium term. There were short-term data reported for mental state using the BPRS and PANSS, no overall differences in mental state were observed between treatment groups. … More research is needed to a) explore the effects of adjunct psychological therapy that is specifically about cannabis and psychosis as currently there is no evidence for any novel intervention being better than standard treatment,for those that use cannabis and have schizophrenia b) decide the most effective drug treatment in treating those that use cannabis and have schizophrenia, and c) assess the effectiveness of cannabidiol in treating schizophrenia. Currently evidence is insufficient to show cannabidiol has an antipsychotic effect.
Die Autoren zieren Leweke et al. 2012:
… the first randomized, double-blind controlled clinical trial demonstrated that in acute schizophrenia cannabidiol exerts antipsychotic properties comparable to the antipsychotic drug amisulpride while being accompanied by a superior, placebo-like side effect profile.
Several lines of experimental and clinical evidence point to a close relationship between cannabis, the endogenous cannabinoid system, and schizophrenia. A variety of animal and human studies found a dysregulation of endocannabinoid signalling in psychosis. Elevated anandamide levels in schizophrenia patients that are negatively correlated with psychotic symptomatology indicate a protective role, whereas 2-arachidonoylglycerol appears to counteract psychosis-related cognitive impairments. Thus, pharmacological manipulation of the endogenous cannabinoid system might be associated with potential antipsychotic properties. In the present systematic review, both preclinical studies using different animal models of psychosis as well as clinical trials investigating the antipsychotic effects of both cannabidiol and rimonabant are presented together with the possible underlying mechanisms of action. The results predominantly confirm the hypothesis of an antipsychotic activity of both cannabinoids. In comparison, cannabidiol appears to be superior to rimonabant with a pharmacological profile similar to atypical antipsychotic drugs.
The current study aimed to determine the impact of marijuana on mood in bipolar patients and to examine whether marijuana confers an additional negative impact on cognitive function. Twelve patients with bipolar disorder who smoke marijuana (MJBP), 18 bipolar patients who do not smoke (BP), 23 marijuana smokers without other Axis 1 pathology (MJ), and 21 healthy controls (HC) completed a neuropsychological battery. Further, using ecological momentary assessment, participants rated their mood three times daily as well as after each instance of marijuana use over a four-week period. Results revealed that although the MJ, BP, and MJBP groups each exhibited some degree of cognitive impairment relative to HCs, no significant differences between the BP and MJBP groups were apparent, providing no evidence of an additive negative impact of BPD and MJ use on cognition. Additionally, ecological momentary assessment analyses indicated alleviation of mood symptoms in the MJBP group after marijuana use; MJBP participants experienced a substantial decrease in a composite measure of mood symptoms. Findings suggest that for some bipolar patients, marijuana may result in partial alleviation of clinical symptoms. Moreover, this improvement is not at the expense of additional cognitive impairment.
First, we consider the role of human genetic factors and cannabis strain chemotypic differences in contributing to interindividual variation in the response to cannabinoids, such as THC, and review studies demonstrating that THC-induced impairments in decision-making processes are mediated by actions at prefrontal CB1 receptors. We further describe evidence that signalling through prefrontal or ventral hippocampal CB1 receptors modulates mesolimbic dopamine activity, aberrations of which may contribute to emotional processing deficits in schizophrenia. Lastly, we review studies suggesting that endocannabinoid tone in the amygdala is a critical regulator of anxiety, and report new data showing that FAAH activity is integral to this response. Together, these findings underscore the importance of cannabinoid signalling in the regulation of cognitive and affective behaviours, and encourage further Research…

Als Vergleich ein Cochrane-Review zu einer zur Behandlung der Schizophrenie zugelassenen Therapie:
Risperidone (depot) for schizophrenia.
Conclusion:
Depot risperidone may be more acceptable than Placebo injection but it is hard to know if it is any more effective in controlling the symptoms of schizophrenia.

Restless-legs Syndrom

Schmerz

Conclusion: Patient-managed cannabis use is associated with clinically significant improvements in self-reported symptom relief for treating a wide range of health conditions, along with frequent positive and negative side effects.

akute Schmerzen:

CONCLUSION:
On the basis of the available randomized controlled trial evidence, cannabinoids have no role in the management of acute pain.

chronische Schmerzen:

CONCLUSION 4-1:
There is substantial evidence that cannabis is an effective treatment for chronic pain in adults.

Neuropathische Schmerzen:

PERSPECTIVE:
This novel Bayesian meta-analysis of individual patient data from 5 randomized trials suggests that inhaled cannabis may provide short-term relief for 1 in 5 to 6 patients with neuropathic pain. Pragmatic trials are needed to evaluate the long-term benefits and risks of this treatment.
Die kanadische Schmerzgesellschaft empfiehlt Cannabinoide als Drittlinientherapie nach Versagen von Antidepressiva oder Antikonvulsiva (Erstlinie) und Versagen von Opioiden (Zweitlinie).
The authors therefore agree with those (eg, Moore et al, 2007) who argue that even without data to demonstrate causation, the potential for long-term brain changes by regular cannabis exposure during adolescence is sufficient to warn the public against the risk of adverse psychiatric outcomes with adolescent cannabis use.
The authors also share concern about the impact of extraordinarily high THC concentrations in new routes of THC administration, such as marijuana e-cigarettes and dabbing (>60%THC), which may heighten the likelihood of adverse psychiatric consequences …
Tetrahydrocannabinol (THC) and pharmaceutical combinations of THC and cannabidiol (nabiximols) show moderate evidence of benefit for chronic neuropathic pain. (From published Erratum in CMAJ. 2017 Aug 28; 189(34): E1099.)
Schlussfolgerungen.
Cannabinoide waren Placebo in der Wirksamkeit geringfügig überlegen, in ihrer Verträglichkeit aber unterlegen.
Hinsichtlich der Sicherheit im Studienzeitraum ergab sich kein Unterschied. Bei ausgewählten Patienten mit neuropathischen Schmerzen können Cannabinoide für eine kurz- und mittelfristige Therapie mit Cannabinoiden bei nicht ausreichendem Effekt von Erst- und Zweitlinientherapien in Betracht gezogen werden.

Als Vergleich ein Cochrane-Review zur Wirksamkeit von Amitryptilin bei neuropathischen Schmerzen:
Amitriptyline for neuropathic pain and fibromyalgia in adults. Cochrane Database Syst Rev. 2012:
AUTHORS' CONCLUSIONS:
Amitriptyline has been a first-line treatment for neuropathic pain for many years. The fact that there is no supportive unbiased evidence for a beneficial effect is disappointing, but has to be balanced against decades of successful treatment in many patients with neuropathic pain or fibromyalgia. There is no good evidence of a lack of effect; rather our concern should be of overestimation of treatment effect…
Zu diesem Cochrane Review (Amitriptyline for neuropathic pain. Cochrane Database Syst Rev. 2015) gibt es ein Update, das zu den gleichen Schlussfolgerungen kommt.
Weiterer Cochrane-Review zum Vergleich:
Gabapentin for chronic neuropathic pain and fibromyalgia in adults. Cochrane Database Syst Rev. 2014:
AUTHORS' CONCLUSIONS:
There was no top tier evidence that was unequivocally unbiased. … Over half of those treated with gabapentin will not have worthwhile pain relief. Results might vary between different neuropathic pain conditions, and the amount of evidence for gabapentin in neuropathic pain conditions except postherpetic neuralgia and painful diabetic neuropathy, and in fibromyalgia, is very limited.
Weiterer Cochrane-Review zum Vergleich:
Levetiracetam for neuropathic pain in adults. Cochrane Database Syst Rev. 2014:
AUTHORS' CONCLUSIONS:
The amount of evidence for levetiracetam in neuropathic pain conditions was very small and potentially biased because of the methods of analysis used in the studies. There was no indication that levetiracetam was effective in reducing neuropathic pain, but it was associated with an increase in participants who experienced adverse events and who withdrew due to adverse events.
Weiterer Cochrane-Review zum Vergleich:
Nortriptyline for neuropathic pain in adults. Cochrane Database Syst Rev. 2015:
AUTHORS' CONCLUSIONS:
We found little evidence to support the use of nortriptyline to treat the neuropathic pain conditions included in this review. There were no studies in the treatment of trigeminal neuralgia. The studies were methodologically flawed, largely due to small size, and potentially subject to major bias.
Weiterer Cochrane-Review zum Vergleich:
Oxycodone for neuropathic pain and fibromyalgia in adults. Cochrane Database Syst Rev. 2014:
AUTHORS' CONCLUSIONS:
No convincing, unbiased evidence suggests that oxycodone (as oxycodone CR) is of value in treating people with painful diabetic neuropathy or postherpetic neuralgia. There is no evidence at all for other neuropathic pain conditions, or for fibromyalgia. Adverse events typical of opioids appear to be common.

Spastik

The study was registered on the EudraCT database with number 2016-001034-10
Conclusion: THC:CBD is used in a wide dose range suggesting that the drug was applied on the basis of individual patients' needs and preferences. Contributing to this notion, moderate to severe spasticity was associated with an elevated number of daily THC:CBD actuations and stronger recommendation rate (NPS) as compared to patients with mild spasticity. Overall, treatment satisfaction (TSQM-9) was high. The results suggest that THC:CBD may serve as a valuable addition in the spectrum of symptomatic therapy in ALS. However, prospective studies and head-to-head comparisons to other spasticity medications are of interest to further explore the effectiveness of THC:CBD in the management of spasticity, and other ALS-related symptoms.

infantile Zerebralparese

auszugsweise deutsche Übersetzung:
"… Wir können aus einer einzigen Studie keine eindeutigen Schlüsse über mangelnde Wirksamkeit ziehen, aber diese Ergebnisse zeigen die Verantwortung der Nabixomols-Befürworter, die für eine bessere Beweislage sorgen sollten. Die Studie war doppelblind, die statistische Aussagekraft war moderat, und es gab keine Trends in den Ergebnissen, die darauf hingedeutet hätten, dass eine größere Studie einen klinisch wichtigen Unterschied festgestellt hätte. Wie bei vielen pädiatrischen Studien bestand auch bei dieser Studie eine Einschränkung darin, dass man sich auf die Bewertung der Patientensymptome durch Betreuungspersonen verließ. Die Autoren erkennen die gewählten Spastizitäts-Messwerte auch als möglichen Schachpunkt ihrer Studie an. …
Die vorliegenden Ergebnisse stimmen mit den bescheidenen Vorteilen von Nabiximols bei Multipler Sklerose überein. Viele Studien fanden keine signifikanten Vorteile bei objektiven Messungen der Spastizität bei Multipler Sklerose; Vorteile zeigten sich vor allem in Messungen von Spastizität oder Schmerzen durch die Patienten selbst. In Australien wurde die Evidenz für Nabiximols bei Multipler Sklerose nicht als ausreichend angesehen, um eine öffentliche Subventionierung der Kosten für dieses Medikament zu rechtfertigen.
… Die aktuelle Studie, vor dem Hintergrund früherer Studien betrachtet, zeigt, dass es keine ausreichende Evidenz für die Verwendung von Cannabinoiden bei pädiatrischer Spastizität außerhalb robuster klinischer Studien gibt."

Sucht

RESULTS:
Cannabis users were more likely to report hazardous alcohol use, use of other illicit drugs, and unauthorized use of prescription drugs than were non-users. Within the group of active cannabis users, frequent cannabis use, compared to occasional use, was associated with the use of other illicit drugs and negatively associated with hazardous alcohol use.
DISCUSSION AND CONCLUSIONS:
The association between cannabis use and hazardous alcohol use, use of other illicit drugs, and unauthorized use of prescription drugs was expected. However, the negative association between frequent cannabis use and hazardous alcohol use among active cannabis users was surprising. This indicates that frequent cannabis users may differ from more occasional users in clinical needs.
Benzodiazepine werden weltweit in Indikationen eingesetzt, in denen es Cannabinoide eine - möglicherweise - weniger riskante Alternative darstellen könnten:
Globally benzodiazepines remain one of the most prescribed medication groups, especially in the primary care setting. With such high levels of prescribing it is not surprising that benzodiazepine dependence is common, cutting across all socioeconomic levels. Despite recognition of the potential for the development of iatrogenic dependence and the lack of any effective treatment, benzodiazepines continue to be widely prescribed in general practice.
CONCLUSIONS:
There is a statistical association between recent cannabis use and lower frequency of nonmedical opioid use among PWID. This may suggest that PWID use cannabis to reduce their pain and/or nonmedical use of opioids. However, more research, including prospective longitudinal studies, is needed to determine the validity of these findings.
CONCLUSIONS:
Transition from use to dependence was highest for nicotine users, followed by cocaine, alcohol and cannabis users. Transition to cannabis or cocaine dependence occurred faster than transition to nicotine or alcohol dependence. The existence of common predictors of transition dependence across substances suggests that shared mechanisms are involved. The increased risk of transition to dependence among individuals from minorities or those with psychiatric or dependence comorbidity highlights the importance of promoting outreach and treatment of these populations.
Epidemiological evidence demonstrates that cannabis use is associated with an increased risk of psychotic outcomes, and confirms a dose-response relationship between the level of use and the risk of later psychosis. High-potency cannabis and synthetic cannabinoids carry the greatest risk. Experimental administration of tetrahydrocannabinol, the active ingredient of cannabis, induces transient psychosis in normal subjects, but this effect can be ameliorated by co-administration of cannabidiol. This latter is a constituent of traditional hashish, but is largely absent from modern high-potency forms of cannabis…
CONCLUSION:
The substitution of one psychoactive substance for another with the goal of reducing negative outcomes can be included within the framework of harm reduction. Medical cannabis patients have been engaging in substitution by using cannabis as an alternative to alcohol, prescription and illicit drugs.
CONCLUSIONS:
There is no clear pattern of outcomes related to cannabis substitution. Most importantly, the recommendation to prescribe alcohol-dependent individuals cannabis to help reduce drinking is premature. Future studies should use longitudinal data to better understand the consequences of cannabis substitution.

Alle Darstellungen medizinischer Sachverhalte, Erkrankungen und Behinderungen und deren sozialmedizinische Einordnung und Kommentierungen hier im Wiki dienen nicht einer "letzt begründenden theoretisch-wissenschaftlichen Aufklärung", sondern sind frei nach Karl Popper "Interpretationen im Licht der Theorien."
Zitat nach: Bach, Otto: ''Über die Subjektabhängigkeit des Bildes von der Wirklichkeit im psychiatrischen Diagnostizieren und Therapieren''. In: Psychiatrie heute, Aspekte und Perspektiven, Festschrift für Rainer Tölle, Urban & Schwarzenberg, München 1994, ISBN 3-541-17181-2, (Zitat: Seite 1)
Alle medizinischen Aussagen und Informationen in diesem Wiki dienen nicht der medizinischen Beratung und können und sollen eine persönliche fachliche ärztliche Beratung nicht ersetzen!



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