Category Archives: Depression

UK medical Cannabis registry: A two-year case series of clinical outcomes in depression

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“Background: Whilst preclinical evidence details the effects of cannabinoids on mood regulation, there is a paucity of clinical evidence on the use of cannabis-based medicinal products (CBMPs) in individuals with depression. This study aims to evaluate longitudinal changes in patient-reported outcome measures (PROMs) and the incidence of adverse events over 24 months in patients treated with CBMPs for depression.

Methods: Patient data from the UK Medical Cannabis Registry were used for analysis. PROMs, including the Patient Health Questionnaire-9 (PHQ-9), Generalised Anxiety Disorder-7 (GAD-7), Single-Item Sleep Quality Scale (SQS), EuroQol 5-Dimension 5-Level (EQ-5D-5L), and Patient Global Impression of Change (PGIC), were measured at baseline, 1, 3, 6, 12, 18, and 24 months. Adverse events (AEs) were also recorded. P < 0.050 was considered statistically significant.

Results: Of the 34,563 patients in the UK Medical Cannabis Registry on January 6th 2025, 698 (2.02 %) patients were included in the analysis. Improvements were observed across the PHQ-9. GAD-7, SQS, and EQ-5D-5L index value at all time points compared to baseline (p < 0.001). At baseline, half of the patients reported severe anxiety (GAD-7 ≥ 15: 50.86 %, n = 355), which was correlated with depression severity (PHQ-9; r = 0.67, p < 0.001). Sixty-three patients (9.03 %) reported at least one AE during treatment, of which 85 % (n = 411) were mild or moderate.

Discussion: Initiation of CBMPs was associated with statistically and clinically significant improvements in depression, anxiety, sleep quality, and health-related quality of life among patients. Improvements were most prominent in the first 3 months. Limitations of the study mean that no causal relationship can be ascertained.

Conclusion: The positive findings from this and other observational data support future evaluation of CBMPs for the treatment of depression to establish their efficacy.”

https://pubmed.ncbi.nlm.nih.gov/41506388

“This UK Medical Cannabis Registry study of patients with treatment-resistant depression prescribed CBMPs demonstrated sustained and clinically meaningful improvements in depression, anxiety, health-related quality of life, and sleep quality over 24 months. Improvements were most pronounced within the first three months and were sustained thereafter. Adverse events were infrequent and predominantly mild to moderate.”

https://www.sciencedirect.com/science/article/pii/S0165032725025728?via%3Dihub

Cannabidiol Alleviates LPS-Induced Depressive-Like Behaviors Via Improving Mitochondria Function

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“Mitochondrial autophagy has been regarded as a new signaling pathway for the action of antidepressant drugs.

The neuroprotective properties of the non-psychoactive cannabinoid cannabidiol (CBD) have been demonstrated in different animal models of neurological disorders. However, the therapeutic effect of cannabidiol on neuroinflammation-induced depression and its underlying molecular mechanisms involved has not been comprehensively studied.

In this study, depressive-like behaviors were induced in male C57BL/6 mice by LPS injection, with intragastric administration of CBD (70 or 140 mg/kg/day) for 6 days.

Our results demonstrated that CBD treatment significantly attenuated lipopolysaccharide (LPS)-induced depressive-like behaviors, accompanied by a marked amelioration of synaptic healthiness in the hippocampal region.

CBD effectively inhibited reactive oxygen species production, normalized the levels of oxidative stress markers, and restored superoxide dismutase activity, involving a mechanism that promotes mitochondrial biogenesis and mitophagy. In addition, LPS-induced neuroinflammation was reduced by CBD, as evidenced by a marked decrease in neuroinflammatory activation markers. CBD also inhibited LPS-activated inflammasome activation by targeting NLRP3/IL-1β/Caspase-1 signaling pathway.

These findings suggest that CBD may be a potential therapeutic drug for managing major depressive disorder.”

https://pubmed.ncbi.nlm.nih.gov/41484536

https://link.springer.com/article/10.1007/s12035-025-05614-w

Neuropathic Pain and Related Depression in Mice: The Effect of a Terpene and a Minor Cannabinoid in Combination

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“Background/Objectives: Neuropathic pain is one of the most severe types of chronic pain. Although it is difficult to manage, it often co-occurs with depression. Yet, no medication addresses the neuropathic pain and depression comorbidity. Therefore, developing integrated treatment strategies that address both pain and depression is a major public health priority and an unmet need affecting millions. 

Methods: In this study, we investigated the effect of combining a terpene, Beta-Caryophyllene (BCP), and cannabidiol (CBD) on neuropathic pain and associated depression. We employed a chronic constriction injury (CCI) neuropathic pain model and a series of behavioral tests to evaluate how oral administration of this combination influences neuropathic pain and depression-like behaviors in mice. We employed immunohistochemistry and proteomics approaches to explore the mechanism. 

Results: The analgesic effect of combining CBD and BCP is synergistic in neuropathic pain and also shows an antidepressant effect. Additionally, we found that this combination decreases neuroinflammation associated with CCI and affects specific genes involved in the inflammation. 

Conclusions: This work provides preclinical scientific evidence supporting the potential usefulness of this combination for neuropathic pain and associated depression.”

https://pubmed.ncbi.nlm.nih.gov/41463111

“Cannabis plants contain various non-psychoactive compounds, including Caryophyllene (BCP). BCP is a natural bicyclic sesquiterpene that acts as a natural ligand for the cannabinoid type 2 receptor (CB2) and is an FDA-approved food additive. It has several benefits, such as pain relief, antidepressant effects, and anti-inflammatory properties.

Given this background, the main goal of this study is to test the hypothesis that combining CBD and BCP is effective for neuropathic pain while also demonstrating antidepressant effects.”

“In conclusion, the proposed project introduces the concept that the combination of CBD and BCP can effectively relieve neuropathic pain while also addressing depression. This knowledge will advance the field by providing preclinical scientific evidence supporting the potential usefulness of this combination for neuropathic pain and associated depression.”

https://www.mdpi.com/2227-9059/13/12/3103


Medicinal use of non-prescribed cannabis: a cross-sectional survey on patterns of use, motives for use, and treatment access in the Netherlands

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“Background: Despite the Netherlands having one of the world’s oldest medical cannabis programs, the majority of people who use cannabis for medicinal purposes continue to rely on non-prescribed sources. This study investigates patterns of use, motives for use, perceived effectiveness, and barriers to accessing prescribed cannabis among individuals self-medicating with non-prescribed cannabis.

Methods: A cross-sectional online survey was conducted between January and April 2023, using convenience sampling primarily via social media. Participants (N = 1059) were adults (18 years or older) residing in the Netherlands who self-reported current use of non-prescribed cannabis-based products to manage physical or mental health symptoms.

Results: Cannabis was used to manage a wide range of conditions, most commonly chronic pain, sleep disorders, depression, and ADHD/ADD, with three out of four participants reporting use for multiple conditions. Most participants obtained cannabis from coffeeshops, although one in four also reported home cultivation as a source. Participants typically smoked cannabis with tobacco, reported (near-)daily use for therapeutic purposes, and indicated a monthly expenditure of €100. The majority was not aware of the THC and CBD content of their products. Perceived effectiveness was rated as high, and more than half of those with a history of prescription medication use reported substituting cannabis for these medications. Only a minority of participants had ever used, or were currently using, prescribed cannabis. Commonly cited barriers included perceived lower quality, higher cost, and lower ease of access compared with non-prescribed cannabis.

Conclusions: The widespread use of non-prescribed cannabis for medicinal purposes in the Netherlands reflects both unmet health needs and barriers within the regulated medical cannabis system. Risky use practices – such as smoking cannabis with tobacco and using products without knowing their cannabinoid content – raise public health concerns. The findings highlight the need for harm reduction strategies and policies that better align medical cannabis regulation with patients’ real-world behaviours and care needs.”

https://pubmed.ncbi.nlm.nih.gov/41331499

https://link.springer.com/article/10.1186/s42238-025-00355-y

The Endocannabinoid System: Pharmacological Targets and Therapeutic Potential in CNS Disorders

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“The endocannabinoid system (ECS) influences a wide range of brain functions, including synaptic transmission, neuroplasticity, emotion, and immune regulation within the central nervous system, with CB1 and CB2 receptors mediating various neurophysiological and pathophysiological outcomes. Thus, growing interest in its therapeutic potential has prompted extensive research into how cannabinoid receptors contribute to the pathophysiology of neurological and psychiatric disorders, particularly CB1 and CB2.

This review has integrated findings from studies published between 2015 and 2025, covering conditions, like depression, anxiety, pain, multiple sclerosis, and Parkinson’s disease. We have also examined recent advances in receptor pharmacology and experimental technologies, including cryo-EM, optogenetics, and chemogenetics.

Although ECS-targeted therapeutics hold considerable promise, some key challenges remain in establishing safe and effective dosing protocols and integrating these approaches into clinical frameworks.

This review has provided an updated perspective on the system’s role in brain health and its potential to inform future therapeutic directions. Thus, ECS-targeted strategies may become increasingly important in managing and treating central nervous system disorders.”

https://pubmed.ncbi.nlm.nih.gov/41178765/

https://www.eurekaselect.com/article/151549

Measuring the Effects of Cannabis on Anxiety and Depression Among Cancer Patients

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“Introduction: Cancer patients are increasingly turning to cannabis products to modulate physical and psychological symptoms despite limited evidence supporting their efficacy. We aimed to explore cancer patients’ self-reported anxiety and depression symptoms in response to cannabis use.

Methods: This longitudinal study examined how patient-reported anxiety and depression symptoms varied according to the dose, ratio of tetrahydrocannabinol (THC) to cannabidiol (CBD), and route of administration of cannabis products among cancer patients. Change in self-reported anxiety and depression symptoms was evaluated in 1962 cancer patients after 30 days of enrollment in the Minnesota Medical Cannabis Program.

Results: Anxiety scores improved more in patients taking higher doses of CBD (> 14.3 mg/day) compared to those taking lower doses (< 4.6 mg/day) and among patients using enteral cannabis products. Depression scores also improved more for patients taking enteral products.

Discussion: Anxiety scores varied according to the dose of cannabis, the ratio of THC to CBD, and the route of administration of cannabis products. In contrast, depression scores only varied according to the route of administration.

Conclusions: This study of cancer patients in Minnesota suggests that patterns of cannabis use that include relatively higher doses of CBD taken enterally may improve the quality of life of cancer survivors who report anxiety and depression. This study constructs a foundation for future research to improve the tailoring of cannabis-related educational materials to patients’ needs and inform the training of healthcare professionals on how to recommend cannabis products for cancer survivors.”

https://pubmed.ncbi.nlm.nih.gov/41163433/

“Given the high prevalence of anxiety and depression symptoms among cancer patients, along with the potential for cannabis products to alleviate these serious psychological symptoms, this study suggests specific patterns of use that may improve the quality of life of cancer survivors.”

https://onlinelibrary.wiley.com/doi/10.1002/cam4.71342

Cannabidiol and Beta-Caryophyllene: chronic inflammatory pain

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“While chronic pain is challenging to manage, it always co-exists with depression. Currently, chronic pain and depression are usually treated separately with distinct approaches, yet effectiveness remains elusive. Consequently, the development of integrated therapeutic strategies for pain while addressing depression is a high public health priority and unmet need that affects millions of people.

This study aims to determine if the combination of the two phytocannabinoids Beta-Caryophyllene (BCP) and cannabidiol (CBD) is effective for chronic pain while simultaneously showing antidepressant effects.

We used a chronic inflammatory pain model (Complete Freund’s Adjuvant, CFA) and a battery of pain and depression-like behavior tests in mice. Proteomics and immunohistochemistry (IHC) were used to explore the potential mechanisms of the effect of the combination on pain and depression.

We found that mice treated with the CBD and BPC combination produced a synergistic pain-relieving effect in the chronic inflammatory pain model and exhibited antidepressant properties.

Our IHC data also show that the CBD and BCP combination significantly reduced the neuroinflammation produced by CFA, and the proteomics showed downregulation of selected proteins involved in inflammation by the combination, compared to the individual effects of CBD and BCP.

In conclusion, our current findings show that, in the CFA pain model, the combination of CBD and BCP produces a synergistic pain-relief effect while also having antidepressant properties. Additionally, our data show that the anti-inflammatory action of this combination may explain its beneficial effects on pain and depression. Therefore, our data suggest this combination as a potentially effective treatment for chronic pain and related depression.”

https://pubmed.ncbi.nlm.nih.gov/41120021/

“In conclusion, our current findings show that, in the CFA pain model, the combination of CBD and BCP produces a synergistic analgesic effect while also having antidepressant properties. Additionally, our data show that the anti-inflammatory action of this combination may explain its beneficial effects on pain and depression. Therefore, our data suggest this combination as a potentially effective treatment for the co-occurrence of chronic pain and depression.”

https://www.sciencedirect.com/science/article/pii/S1043661825004128?via%3Dihub

Cannabidiol reverses depression-like behaviors by enhancing hippocampal synaptic plasticity in rats with chronic restraint stress

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“Background and aim: Major depressive disorder is a prevalent psychiatric condition associated with impaired neuroplasticity, particularly in the hippocampus. Although selective serotonin reuptake inhibitors (SSRIs) are commonly prescribed, their delayed onset and adverse effects highlight the need for alternative therapies. Cannabidiol (CBD), a non-psychotomimetic cannabinoid, has shown antidepressant-like properties, but its mechanistic link to hippocampal synaptic plasticity remains unclear. This study aimed to evaluate the effects of CBD on depression-like behaviors and hippocampal neuroplasticity in rats subjected to chronic restraint stress (CRS).

Materials and methods: Sixty male Wistar rats were randomly divided into six groups: Non-stressed vehicle (NV), CRS vehicle (SV), escitalopram-treated CRS (SE, 10 mg/kg), and CBD-treated CRS at 10, 30, or 100 mg/kg (SC10, SC30, and SC100). Rats were subjected to CRS for 28 days and treated daily through intraperitoneal injection. Depression-like behaviors were assessed using the forced swim test (FST) and sucrose preference test (SPT). Locomotor activity was evaluated through the open-field test (OFT). Hippocampal dendritic spine density (Golgi-Cox staining) and long-term potentiation (LTP, electrophysiology) were measured on day 28.

Results: CRS induced behavioral despair (↑ immobility in FST) and anhedonia (↓ sucrose preference in SPT), accompanied by reduced hippocampal spine density. At all doses, CBD significantly reduced immobility, comparable to escitalopram. Notably, only CBD at 100 mg/kg and escitalopram reversed anhedonia. All CBD-treated groups showed an increase in dendritic spine density, with SC10 producing the greatest enhancement. Moreover, CBD at 100 mg/kg markedly improved hippocampal LTP at 1 h and 2 h post-stimulation, an effect not observed with escitalopram. Locomotor activity remained unaffected.

Conclusion: CBD demonstrated potent antidepressant-like effects in a CRS rat model, alleviating behavioral despair and anhedonia while enhancing hippocampal dendritic spine density and synaptic strength. These findings suggest CBD as a promising candidate for stress-related mood disorders, with mechanistic actions distinct from conventional SSRIs and potential utility in patients unresponsive to current therapies.”

https://pubmed.ncbi.nlm.nih.gov/41113223/

https://veterinaryworld.org/Vol.18/September-2025/22.php

A novel cannabidiol:tetramethylpyrazine cocrystal (CBD:TMP, ART12.11) improves the efficacy and bioavailability of cannabidiol in reducing stress-induced depressive and anxiety symptoms

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“Clinical and pre-clinical research has reported promising outcomes for cannabidiol (CBD) in treating mood and anxiety disorder symptoms. However, the pharmacokinetic properties of CBD, such as low and variable bioavailability and low aqueous solubility, limit its therapeutic applications.

This study investigated the effects of ART12.11, a novel cannabidiol:tetramethylpyrazine (CBD:TMP) cocrystal, that aims to improve the pharmacotherapeutic potential of CBD by combining it with the co-former tetramethylpyrazine (TMP) to improve CBD’s pharmaceutical properties.

We used an integrative combination of translational behavioural pharmacology alongside targeted gene and protein expression analyses to characterize the potential anti-depressant and anxiolytic-like effects of ART12.11 in male Sprague Dawley rats, following exposure to chronic stress. In addition, we investigated blood plasma concentrations of CBD and TMP following oral administration of ART12.11 to examine bioavailability.

We report that oral administration of ART12.11 reversed stress-induced behavioural deficits and produced significant anti-depressant and anxiolytic-like behavioural effects, which were superior to oral administration of CBD alone, TMP alone, or the co-administration of a non-crystalline mixture of CBD and TMP. Further, we report that ART12.11 resulted in higher blood plasma levels of CBD and its major metabolite, indicating superior bioavailability. Finally, we demonstrate that ART12.11 increased activation of the endocannabinoid and serotonergic systems directly in the prefrontal cortex, ventral hippocampus, and nucleus accumbens.

Collectively, our findings indicate that ART12.11 may offer significant advantages over delivering CBD by more traditional approaches in the treatment of mood and anxiety disorders.”

https://pubmed.ncbi.nlm.nih.gov/40854502/

https://www.sciencedirect.com/science/article/abs/pii/S0278584625002325?via%3Dihub

Acute and chronic effects of medicinal cannabis use on anxiety and depression in a prospective cohort of patients new to cannabis

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“Introduction: Medicinal cannabis has mixed evidence for treating anxiety and depression, yet patients frequently use it as a treatment. This observational study evaluated the effects of medicinal cannabis initiation in adults with clinically significant anxiety and/or depression over a 6-month period.

Methods: Adults with clinically significant anxiety and/or depression initiating medicinal cannabis use in Maryland, USA completed ecological momentary assessment (EMA) and longitudinal follow-up evaluations. Hospital Anxiety and Depression Scale (HADS) assessments were completed at baseline and 1, 3, and 6 months after medicinal cannabis initiation. EMA measures were completed at baseline and daily for 8 weeks after cannabis initiation with measures collected before each cannabis use and at time of expected peak effect. Changes in anxiety and depression were evaluated using linear mixed effect models.

Results: Significant decreases from baseline in anxiety and depression were observed, with mean scores dropping below clinically significant levels within three months of initiation. EMA data indicated that most participants selected THC-dominant cannabis and acute reductions in anxiety, depression, and perceived driving ability along with increased ratings of feeling “high”. Acute effects were dose-dependent: 10-15 mg of oral THC and at least 3 puffs of vaporized cannabis yielded the most robust reductions in anxiety and depression.

Conclusions: Initiation of THC-dominant medicinal cannabis was associated with acute reductions in anxiety and depression, and sustained reductions in overall symptom severity over a 6-month period. Controlled clinical trials are needed to further investigate the efficacy and safety of medicinal cannabis for acute anxiety and depression symptom management.”

https://pubmed.ncbi.nlm.nih.gov/40623642/

“In this prospective, observational study, medicinal cannabis use was associated with significant decreases in self-reported anxiety and depression compared with pre-cannabis use initiation baseline assessments among individuals with clinically significant anxiety and/or depression. Reductions in anxiety and depression were observed acutely following individual episodes of cannabis use and overall symptom reductions were sustained over the six-month period of observation.”

https://www.sciencedirect.com/science/article/abs/pii/S0165032725012716?via%3Dihub