cannabidiol and Depressive-Disorder

Three Cannabis Based Medicinal Extracts (CBMEs) for sublingual use became available in 2000. A total of 34 'N of 1' studies were undertaken using this novel therapy for patients with chronic, mainly neuropathic, pain and associated symptoms to explore efficacy, tolerability, safety and dosages. Three CBMEs (Delta9 Tetrahydrocannabinol (THC), Cannabidiol (CBD) and a 1:1 mixture of them both) were given over a 12-week period. After an initial open-label period, the CBMEs were used in a randomised, double-blind, placebo controlled, crossover trial. Extracts which contained THC proved most effective in symptom control. Regimens for the use of the sublingual spray emerged and a wide range of dosing requirements was observed. Side-effects were common, reflecting a learning curve for both patient and study team. These were generally acceptable and little different to those seen when other psycho-active agents are used for chronic pain. These initial experiences with CBME open the way to more detailed and extensive studies.

Topics: Administration, Sublingual; Adult; Aged; Analgesics, Non-Narcotic; Cannabidiol; Chronic Disease; Cross-Over Studies; Depressive Disorder; Double-Blind Method; Dronabinol; Drug Combinations; Female; Humans; Male; Middle Aged; Multiple Sclerosis; Pain; Pain Measurement; Patient Selection; Sleep; Treatment Outcome

The current study explores the therapeutic potential of Cannabidiol (CBD), a compound in the Cannabis plant, using both sexes of 2 "depressive-like" genetic models, Wistar Kyoto (WKY) and Flinders Sensitive Line (FSL) rats. Rats ingested CBD (30 mg/kg) orally. In the saccharin preference test, following a previous report of a pro-hedonic effect of CBD in male WKY, we now found similar results in female WKY. CBD also decreased immobility in the forced swim test in males (both strains) and in female WKY. These findings suggest a role for CBD in treating mental disorders with prominent symptoms of helplessness and anhedonia.

Topics: Animals; Antidepressive Agents; Cannabidiol; Depressive Disorder; Disease Models, Animal; Female; Food Preferences; Male; Motor Activity; Rats; Rats, Inbred WKY; Saccharin; Swimming

Cannabidiol (CBD) is a compound of Cannabis sativa with relevant therapeutic potential in several neuropsychiatric disorders including depression. CBD treatment has shown significant antidepressant-like effects in different rodent preclinical models. However, the mechanisms involved in CBD-induced antidepressant effects are still poorly understood. Therefore, this work aimed at investigating the participation of serotonin (5-HT) and/or noradrenaline (NA) in CBD-induced antidepressant-like effects in the forced swimming test (FST) by: 1) testing if CBD co-administration with serotonergic (fluoxetine, FLX) or noradrenergic (desipramine, DES) antidepressants would have synergistic effects; and 2) investigating if 5-HT or NA depletion would impair CBD-induced behavioral effects. Results showed that CBD (10 mg/kg), FLX (10 mg/kg) and DES (5 mg/kg) induced antidepressant-like effects in mice submitted to FST. Ineffective doses of CBD (7 mg/kg), when co-administered with ineffective doses of FLX (5 mg/kg) or DES (2.5 mg/kg) resulted in significant antidepressant-like effects, thus implicating synergistic and/or additive mechanisms. Pretreatment with PCPA (an inhibitor of serotonin synthesis: 150 mg/kg, i.p., once per day for 4 days), but not DSP-4 (a noradrenergic neurotoxin: 1 μg/μl, i.c.v., 24 h before the test), reduced monoamine levels in the brain. However, only PCPA treatment abolished CBD-induced behavioral effects in FST, indicating the participation of serotonergic mechanisms. None of the treatments induced locomotor effects. Our results suggest that the antidepressant-like effect induced by CBD in the FST is dependent on serotonin levels in the central nervous system (CNS).

Topics: Animals; Antidepressive Agents; Brain; Cannabidiol; Depressive Disorder; Desipramine; Disease Models, Animal; Drug Synergism; Fluoxetine; Male; Mice; Norepinephrine; Random Allocation; Serotonin

Cannabidiol (CBD), the main non-psychotomimetic component of marihuana, exhibits anxiolytic-like properties in many behavioural tests, although its potential for treating major depression has been poorly explored. Moreover, the mechanism of action of CBD remains unclear. Herein, we have evaluated the effects of CBD following acute and chronic administration in the olfactory bulbectomy mouse model of depression (OBX), and investigated the underlying mechanism. For this purpose, we conducted behavioural (open field and sucrose preference tests) and neurochemical (microdialysis and autoradiography of 5-HT1A receptor functionality) studies following treatment with CBD. We also assayed the pharmacological antagonism of the effects of CBD to dissect out the mechanism of action. Our results demonstrate that CBD exerts fast and maintained antidepressant-like effects as evidenced by the reversal of the OBX-induced hyperactivity and anhedonia. In vivo microdialysis revealed that the administration of CBD significantly enhanced serotonin and glutamate levels in vmPFCx in a different manner depending on the emotional state and the duration of the treatment. The potentiating effect upon neurotransmitters levels occurring immediately after the first injection of CBD might underlie the fast antidepressant-like actions in OBX mice. Both antidepressant-like effect and enhanced cortical 5-HT/glutamate neurotransmission induced by CBD were prevented by 5-HT1A receptor blockade. Moreover, adaptive changes in pre- and post-synaptic 5-HT1A receptor functionality were also found after chronic CBD. In conclusion, our findings indicate that CBD could represent a novel fast antidepressant drug, via enhancing both serotonergic and glutamate cortical signalling through a 5-HT1A receptor-dependent mechanism.

Topics: Animals; Anti-Anxiety Agents; Antidepressive Agents; Behavior, Animal; Cannabidiol; Depressive Disorder; Disease Models, Animal; Glutamic Acid; Male; Mice; Mice, Inbred C57BL; Olfactory Bulb; Prefrontal Cortex; Receptor, Serotonin, 5-HT1A; Serotonin; Synaptic Transmission

Accumulating evidence suggests that cannabidiol (CBD) may be an effective and safe anxiolytic agent and potentially also an antidepressant.. The objective of this study was to further examine these properties of CBD using the 'depressive-like' Wistar-Kyoto (WKY) rat, focusing on the drug's effect on anhedonia-like behaviors.. Forty-eight WKY and 48 control Wistar adult male rats were pretreated orally with CBD (15, 30 and 45 mg/kg) or vehicle. The saccharin preference test (SPT), the elevated plus maze (EPM) test and the novel object exploration (NOE) test were used.. CBD showed a prohedonic effect on the WKY rats at 30 mg/kg in the SPT. In the NOE, CBD increased exploration of the novel object and locomotion at 45 mg/kg and increased locomotion at 15 mg/kg, indicating an improvement in the characteristically low motivation of WKY rats to explore. There was no similar effect at any dose in the EPM or in open-field behavior in the habituation to the NOE.. These findings extend the limited knowledge on the antidepressant effect of CBD, now shown for the first time in a genetic animal model of depression. These results suggest that CBD may be beneficial for the treatment of clinical depression and other states with prominent anhedonia.

Topics: Analysis of Variance; Anhedonia; Animals; Antidepressive Agents; Anxiety; Cannabidiol; Depressive Disorder; Disease Models, Animal; Dose-Response Relationship, Drug; Exploratory Behavior; Food Preferences; Male; Motor Activity; Rats, Inbred WKY; Rats, Wistar; Saccharin

Cannabidiol (CBD) is a major Cannabis sativa constituent, which does not cause the typical marijuana psychoactivity. However, it has been shown to be active in a numerous pharmacological assays, including mice tests for anxiety, obsessive-compulsive disorder, depression and schizophrenia. In human trials the doses of CBD needed to achieve effects in anxiety and schizophrenia are high. We report now the synthesis of 3 fluorinated CBD derivatives, one of which, 4'-F-CBD (HUF-101) (1), is considerably more potent than CBD in behavioral assays in mice predictive of anxiolytic, antidepressant, antipsychotic and anti-compulsive activity. Similar to CBD, the anti-compulsive effects of HUF-101 depend on cannabinoid receptors.

Topics: Animals; Anti-Anxiety Agents; Antidepressive Agents; Antipsychotic Agents; Anxiety; Anxiety Disorders; Behavior, Animal; Cannabidiol; Depression; Depressive Disorder; Disease Models, Animal; Male; Mice; Motor Activity; Schizophrenia