Table II.
Therapy Studies Evaluating Clinical Response of CBD in Animals and Patients with Different Medical Conditions
| References | Study Design | Subjects | Treatment | Outcomes |
|---|---|---|---|---|
| Epilepsy | ||||
| Devinsky et al., 2017 [3] | Randomized, double-blind, placebo-controlled study | Children and young adults with Dravet syndrome and drug-resistant seizures (n = 120) | 20 mg/kg CBD (p.o.) or placebo daily for 14 weeks, in addition to standard antiepileptic treatment | Reduction in frequency of convulsive seizures by 38.9% per month in CBD group, as compared to 13.3% in placebo group; Overall patients’ condition, assessed with CGIC, improved in 62% of CBD group, as compared to 34% of placebo group |
| Scheffer et al., 2021 [68] | Open-label extension study | Subjects with Dravet syndrome who completed in previous studies (n = 315) | 20–30 mg/kg CBD (p.o.) daily based on response and tolerability, in addition to standard antiseizure medications | Long term use of CBD reduced monthly convulsive (45–74%) and total seizures (49–84%) frequency for up to 156 weeks; Improvement in overall condition in more than 83% of patients, assessed with S/CGIC |
| Devinsky et al., 2018 [52] | Phase 3, randomized, double-blind, placebo-controlled study | Subjects with Lennox-Gastaut syndrome (n = 225) | 10, 20 mg/kg CBD (p.o.) or placebo in two equally divided doses daily for 14 weeks, in addition to standard antiepileptic treatment | Reduction in drop-seizure frequency by 41.9% and 37.2% in 20 and 10 mg CBD group respectively, as compared to 17.2% in placebo group; Overall patients’ condition, assessed with S/CGIC, improved in 57% (20 mg) and 66% (10 mg) of CBD group, as compared to 44% of placebo group |
| Patel et al., 2021 [69] | Open-label extension study | Subjects with Lennox-Gastaut syndrome who completed in previous studies (n = 366) | 20–30 mg/kg CBD (p.o.) daily based on response and tolerability, in addition to standard antiseizure medications | Long term use of CBD resulted in sustained reduction in drop (48–71%) and total seizures (48–68%) frequency for up to 156 weeks; Improvement in overall condition in more than 87% of patients, assessed with S/CGIC |
| Hess et al., 2016 [4] | Expanded-access study | Subjects with treatment-resistant epilepsy associated with tuberous sclerosis complex (n = 18) | Maximum of 50 mg/kg CBD (p.o.) or placebo daily for 12 months | Reduction in weekly seizure frequency by 48.8% after 3 months of CBD treatment; Improvements in cognitive and behavioral function in 85.7% and 66.7% of patients respectively |
| Thiele et al., 2021 [67] | Phase 3, randomized, double-blind, placebo-controlled parallel group study | Subjects with seizures associated with tuberous sclerosis complex (n = 224) | 25 or 50 mg/kg CBD (p.o.) or placebo daily for 16 weeks | Reduction in seizures associated with tuberous sclerosis complex by 48.6% and 47.5% in 25 and 50 mg CBD group respectively, as compared to 26.5% in placebo group |
| Thiele et al., 2022 [70] | Open-label extension study | Subjects with seizures associated with tuberous sclerosis complex (n = 199) | 25–50 mg/kg CBD (p.o.) daily based on response and tolerability | Long term use of CBD reduced seizures associated with tuberous sclerosis complex by 54–68% and sustained through 48 weeks of treatment; Improvement in overall condition in 87% of patients at 26 weeks, assessed with S/CGIC |
| Pain | ||||
| Brioschi et al., 2020 [54] | Animal study | Client-owned dogs with osteoarthritis and associated signs of joint dysfunction (n = 21) | 2 mg/kg of oral transmucosal CBD oil every 12 h or only controlled drugs (firocoxib or prednisone) for 12 weeks | A decrease in Pain Severity Score and Pain Interference Score, as well as an increase in Quality of Life Index were observed in CBD group than in control group, as assessed with CBPI questionnaire completed by the owners |
| Philpott et al., 2017 [72] | Animal study | Wistar rats | 100–300 g CBD (i.a.) or vehicle | 300 g CBD acted locally in the joint and reduced joint mechanical pain and inflammation, resulted in improvement in withdrawal threshold and weight bearing; No effect was shown at low dose CBD (100 and 200 µg) |
| Mejia et al., 2021 [73] | Prospective, randomized, double-blind, placebo-controlled, cross-over pilot animal study | Client-owned dogs with naturally occurring osteoarthritis of appendicular joints (n = 23) | 2.5 mg/kg CBD (p.o.) or placebo every 12 h for 6 weeks | No significant changes in pain severity score between CBD and placebo group, assessed with objective gait analysis, activity counts and clinical metrology |
| Cunetti et al., 2018 [53] | Open-label study | Kidney transplant patients with chronic pain (fibromyalgia, osteoarticular, or neuropathic pain) who requested CBD for pain treatment (n = 7) | 150 mg CBD (p.o.) twice daily for 3 weeks (titrated from 50 mg) | A decreased in pain score index and pain limitation perception were shown in 6 out of 7 patients, leading to partial or total pain improvements |
| Bebee et al., 2021 [74] | Randomized, double-blind, placebo-controlled study | Patients who presented with acute, non-traumatic low back pain (n = 100) | 400 mg single-dose CBD (p.o.) or placebo | No significant reduction in pain score (CBD vs placebo: 6.2 vs 5.8 points) or hospital length of stay (CBD vs placebo: 9.0 vs 8.5 h) for people seeking help at a hospital emergency department for acute low back pain |
| Dieterle et al., 2022 [75] | Randomized, double-blind, placebo-controlled, cross-over study | Healthy participants (n = 24) | 1600 mg single-dose CBD (p.o.) or placebo | No significant difference on opioid-induced hyperalgesia, allodynia, or pain between CBD and placebo group |
| Parkinson's disease | ||||
| Lastres-Becker et al., 2005 [78] | Animal study | Sprague–Dawley rats, injected with 6-hydroxydopamine | 3 mg/kg CBD (i.p.) daily for 2 weeks | CBD showed an increase in the dopamine level in the brain |
| Chagas et al., 2014 [55] | Randomized, double-blind, placebo-controlled study | Subjects with Parkinson’s disease but without dementia or comorbid psychiatric conditions (n = 21) | 75 or 300 mg CBD (p.o.) or placebo daily for 6 weeks | Improvement in daily living activities or well-being from 300 mg CBD in PDQ-39 but did not alter clinical motor symptoms as assessed with UPDRS |
| Leehey et al., 2020 [56] | Open-label study | Subjects with Parkinson’s disease (n = 13) | Epidiolex (titrated from 5 to 20–25 mg/kg) daily for 10–15 days | Improvements in total and motor functions of patients by 17.8% and 24.7%, respectively; Improvements in night-time sleep and emotional or behavioral dyscontrol scores by 49.1% and 10.6%, respectively, assessed with UPDRS |
| Alzheimer's disease | ||||
| Esposito et al., 2007 [82] | Animal study | C57BL/6 J mice, injected with Aβ | 2.5 or 10 mg/kg CBD (i.p.) or vehicle (Tocrisolve 100) daily for 7 days | Dose-dependent inhibition of GFAP mRNA (-31.3 and -81%) and protein expression (-31 and -64.1%), as well as inhibition of iNOS (-33.3 and -61.5%) and IL-1β protein expression (-30.5 and -68%), and the related NO (-30 and -51%) and IL-1β release (-31 and -46.7%) in CBD group |
| Martin-Moreno et al., 2011 [57] | Animal study | C57BL/6 J mice, injected with Aβ | 20 mg/kg CBD (i.p.) or vehicle daily for 1 week, then 3 days/week for 2 weeks | Prevention of both Aβ-induced cognitive impairment as tested with Morris water maze, and the increased gene expression of IL-6 but not TNF-α in CBD group |
| Cheng et al., 2014 [58] | Animal study | APPswe/PS1ΔE9 double transgenic C57BL/6 J × C3H/HeJ mice or wild type-like mice (n = 45) | 20 mg/kg CBD (i.p.) or vehicle (control) daily for 3 weeks | Improvements in social recognition and object recognition memory in the CBD-treated transgenic mice, as assessed with SPT and NORT |
| Huntington’s disease | ||||
| Consroe et al., 1991 [84] | Randomized, double-blind, placebo-controlled, cross-over study | Subjects with Huntington’s disease (n = 15) | 10 mg/kg CBD (p.o.) or placebo daily for 6 weeks | No significant difference in the improvement in chorea severity or other symptoms between CBD and placebo group |
| Depression | ||||
| Xu et al., 2019 [86] | Animal study | ICR mice (n = 48) | 10 mg/kg CBD (i.v.) or 10 or 100 mg/kg CBD (p.o.) for 21 days | Low-dose IV and high-dose oral CBD showed a shorter mobility time (around 200 s) in forced swim test; Chronic use of CBD also appeared to reverse the depression-induced symptoms of chronic stress |
| Solowij et al., 2018 [59] | Open-label study | Frequent cannabis users (n = 20) | 200 mg CBD (p.o.) daily for 10 weeks, while subjects continued usual usage of cannabis | Reduction in BDI score (BL 2.5 vs PT 0.5), improvement in RAVLT performance (Total words recalled from BL 52.55 to PT 56.00) and AST (Latency switching trials from BL 600.63 to PT 549.3 ms), showing an improvement in depressive and cognitive symptoms |
| Allsop et al., 2014 [87] | Randomized, double-blind, placebo-controlled study | Cannabis-dependent treatment seekers (n = 51) | Nabiximols (up to 86.4 mg THC and 80 mg CBD) or placebo for 6 days | Reduction in withdrawal-related depression (from BL 2.78 to abstinence 2.04) and other symptoms like sleep difficulty (from BL 2.95 to abstinence 2.79), restlessness (from BL 3.44 to abstinence 2.8), and decreased appetite (from BL 3.56 to abstinence 2.12) in treatment group |
| Berger et al., 2022 [60] | Open-label, single-arm phase II trial | Young people with anxiety disorders who did not respond to standard treatment with CBT and/or antidepressant (n = 31) | Up to 800 mg CBD (p.o.) daily for 12 weeks, in addition to standard treatment | Significant improvement in depressive symptoms, assessing using QIDS-A17 (BL 11.7 vs PT 8.2) |
| Anxiety | ||||
| Fogaca et al., 2018 [88] | Animal study | Chronically stressed C57BL/6 J mice and wistar rats | 30 mg/kg CBD (i.p.) for 14 days | CBD prevented anxiogenic and depressogenic-like behaviors in EPM and NSF tests and displayed a neuroprotective effect |
| Resstel et al., 2009 [89] | Animal study | Wistar rats | 1, 10 or 20 mg/kg single-dose CBD (i.p.) administered 30 min before exposure to restraint | Reduction of cardiovascular responses induced by restraint stress and attenuation of anxiogenic-like responses in EPM test |
| Guimarães et al., 1990 [91] | Animal study | Wistar rats | 2.5, 5, 10 or 20 mg/kg single-dose CBD (i.p.) administered 60 min before EPM test | Significant increase in the entry ratio in EPM test at lower doses of CBD (2.5, 5 and 10 mg/kg) which showed anxiolytic-like effect of CBD; It also demonstrated inverted U shape dose–effect curve, with highest anxiolytic effect at 5 mg/kg |
| Zuardi et al., 1993 [90] | Randomized, double-blind, placebo-controlled study | Healthy subjects (n = 40) | 300 mg CBD (p.o.), 10 mg diazepam, or 5 mg ipsapirone administered before SPS test | CBD reduced anxiety level after the SPS test, assessed using VAMS anxiety factor |
| Bergamaschi et al., 2011 [61] | Randomized, double-blind, placebo-controlled study | Treatment naïve subjects with generalized SAD (n = 24) and healthy control subjects (n = 12) | 600 mg single-dose CBD (p.o.) or placebo administered 150 min before SPS test | CBD reduced symptoms of anxiety, cognitive impairment, and discomfort caused by public speech and decreased alertness during anticipatory speech in SAD subjects |
| Linares et al., 2019 [92] | Randomized, double-blind, placebo-controlled study | Healthy subjects (n = 57) | 150, 300, 600 mg single-dose CBD (p.o.) or placebo | Significant anxiolytic effects in a SPS test with 300 mg CBD, assessed using VAMS anxiety factor; No significant differences in VAMS scores with 150 and 600 mg CBD |
| Zuardi et al., 2017 [93] | Randomized, double-blind, placebo-controlled study | Healthy subjects, with no history of past or current psychiatric illness, alcohol, or other drug dependence (n = 60) | 100, 300, 900 mg single-dose CBD (p.o.), 1 mg clonazepam (p.o.) or placebo administered 150 min before SPS test | Dose-dependent anxiolytic effects in a SPS test assessed using VAMS anxiety factor, where anxiety levels reduced with 300 mg CBD, but not with 100 and 900 mg, in the post-speech phase |
| Berger et al., 2022 [60] | Open-label, single-arm phase II trial | Young people with anxiety disorders who did not respond to standard treatment with CBT and/or antidepressant (n = 31) | Up to 800 mg CBD (p.o.) daily for 12 weeks, in addition to standard treatment | Significant reduction in anxiety, assessing using OASIS (BL 10.8 vs PT 6.3) and HARS (BL 21.9 vs PT 11.3) |
| Masataka, 2019 [94] | Randomized, double-blind, placebo-controlled study | Japanese teenagers with social anxiety disorder and avoidant personality disorder (n = 37) | 300 mg CBD (p.o.) or placebo daily for 4 weeks | A reduction in FNE (CBD vs placebo: -5.2 vs -0.2) and LSAS score (CBD vs placebo: -12.1 vs -3.1), showing a significant decrease in anxiety in CBD group |
| Hundal et al., 2018 [95] | Randomized, double-blind, placebo-controlled study | Non-clinical subjects with high paranoid traits (n = 32) | 600 mg single-dose CBD (p.o.) or placebo, administered 130 min before entering virtual reality | Increased anxiety in BAI (BL 2.1 vs PT 6.8); No significant difference on persecutory ideation (CBD vs placebo: 13.4 vs 11.1 in SSPS) and physiological effects (cortisol and cardiovascular responses) |
| Arndt et al., 2017 [96] | Randomized, double-blind, placebo-controlled study | Healthy, drug-free subjects (n = 38) | 300, 600 or 900 mg single-dose CBD (p.o.) or placebo | No significant reduction and difference on the responses to negative emotional stimuli and subjective effects between CBD and placebo group |
| Psychosis | ||||
| Hallak et al., 2010 [101] | Double-blind, placebo-controlled study | Subjects with schizophrenia (n = 28) | 300 or 600 mg single-dose CBD (p.o.) or placebo administered 60 min before the assessment | No significant improvements on selective attention in both CBD groups in SCWT |
| Boggs et al., 2018 [100] | Randomized, double-blind, placebo-controlled parallel group, fixed-dose study | Subjects with chronic schizophrenia (n = 41) | 600 mg CBD (p.o.) or placebo daily for 6 weeks, in addition to regular antipsychotic treatment | No significant improvement in psychotic symptoms and cognitive performance in CBD group, assessed using PANSS and MCCB scores respectively |
| McGuire et al., 2018 [62] | Randomized, double-blind, placebo-controlled parallel group study | Subjects with schizophrenia (n = 88) | 1000 mg CBD (p.o.) or placebo daily for 6 weeks, in addition to regular antipsychotic treatment | Reduction in PANSS positive score by 1.4 in CBD group but no significant improvement in cognitive performance and overall functioning, assessed using BACS and GAF |
| Leweke et al., 2012 [28] | Phase 2, randomized, double-blind, parallel-controlled study | Subjects with schizophrenia and schizophreniform psychosis (n = 42) | Up to 800 mg CBD (p.o.) or 800 mg amisulpride (p.o.) daily for 4 weeks | Reduction in PANSS total score by 30.5 and 30.1 in CBD and amisulpride group respectively, showing similar efficacy of both in treating psychotic symptoms. CBD showed fewer extrapyramidal symptoms, less weight gain, and lower prolactin increase |
| Zuardi et al., 2009 [102] | Open-label pilot study | Subjects with Parkinson’s disease who had psychosis for at least 3 months (n = 6) | Flexible dose of CBD (p.o.) (initiated with 150 mg daily) for 4 weeks, in addition to usual therapy | Rapid onset of antipsychotic effects with an improvement in BPRS total score (from 18.5 to 5.5), PPQ total score (from 13 to 1.5), while not worsening symptoms of parkinsonism and cognitive function (UPDRS total score from 67.5 to 51.5; CGI-Improvement from 4 to 1.5) |
| Substance use disorders | ||||
| Ren et al., 2009 [105] | Animal study | Long-Evans rats | 5 or 20 mg/kg CBD (i.p.) | Attenuation of cue-induced heroin seeking behavior. Protracted effect showed after 24 h and 2 weeks post-administration. No effects on heroin self-administration and extinction behavior |
| Parker et al., 2004 [108] | Animal study | Experimentally naive Sprague–Dawley rats | 5 mg/kg CBD (i.p.) or vehicle administered prior to cocaine- and amphetamine-induced conditioned place preference | Less time spent on the cocaine- and amphetamine-paired floor, indicating that CBD potentiated the extinction of both cocaine- and amphetamine-induced conditioned place preference learning in CBD group |
| Viudez-Martinez et al., 2018 [115] | Animal study | C57BL/6 J mice | 30, 60 or 120 mg/kg CBD (i.p.) daily | Reduction in ethanol consumption (from about 6 g of pure ethanol/kg body weight/day to 3.5 g/kg/day) and preference (from 75 to 55%), and hypothermia and handling-induced convulsion |
| Gonzalez-Cuevas et al., 2018 [116] | Animal study | Wistar rats with alcohol or cocaine self-administration histories (n = 24) | Transdermal CBD (2.5 g/100 g gel) or vehicle at 24 h intervals for 7 days | Attenuation of context-induced drug seeking for up to 5 months post-treatment, reduction in experimental anxiety and prevention in impulsivity associated with alcohol dependence in CBD group |
| Solowij et al., 2018 [59] | Open-label study | Frequent cannabis users (n = 20) | 200 mg CBD (p.o.) daily for 10 weeks, while subjects continued usual usage of cannabis | Reduction in CEQ euphoria levels associated with cannabis use (BL 43.75 vs PT 38.65) but no significant changes in the frequency (BL 25 vs PT 30 days per month) and quantity of cannabis use (BL 123.75 vs PT 105.0 cones) |
| Hurd et al., 2019 [106] | Randomized, double-blind, placebo-controlled pilot study | Subjects with opioid dependence, abstinent for at least 7 days (n = 42) | 400, 800 mg CBD (p.o.) or placebo daily for 3 consecutive days | Reduction in the cue-induced heroin craving (mean difference in VAS-C score for placebo vs 400 mg vs 800 mg: 0.93 vs 0.44 vs 0.23) and anxiety (mean difference in VAS-A score for placebo vs 400 mg vs 800 mg: 0.97 vs 0.48 vs 0.24). Protracted effect showed after 24 h and 7 days post-administration |
| Mongeau-Perusse et al., 2021 [110] | Phase 2, randomized, double-blind, placebo-controlled parallel-group study | Subjects with moderate-to-severe cocaine use disorder (n = 78) | 800 mg CBD (p.o.) or placebo daily for 12 weeks | No reduction in cocaine-cue-induced craving and prevention in relapse, as seen from an increased craving scores (CBD vs placebo: 4.69 vs 3.21), and a shorter times-to-cocaine relapse (CBD vs placebo: 4 vs 7 days) |
| Morgan et al., 2013 [112] | Randomized, double-blind, placebo-controlled study | Regular smokers (> 10 cigarettes/day) who wished to stop smoking (n = 24) | 400 μg of inhaled CBD or placebo for 7 days, administered when subjects felt the urge to smoke | Reduction in cigarette consumption (pre-treatment 90 vs PT 50 cigarettes/week) without increased in nicotine craving (TCQ Day 0 43.83 vs Day 7 37.08) in CBD group |
| Hindocha et al., 2018 [113] | Randomized, double-blind, placebo-controlled, cross-over study | Non-treatment seeking, nicotine-dependent cigarette smokers (n = 30) | 800 mg single-dose CBD (p.o.) or placebo, followed by overnight abstinent sessions | Reduction in salience and pleasantness of cigarette cues (valence bias of CBD vs placebo: 0.59 vs 1.10) in CBD group; No significant effects on tobacco craving or symptoms of withdrawal |
| Karoly et al., 2021 [117] | Observational study | Cannabis and alcohol using adults (n = 120) | One of the three cannabis products (THC-dominant, CBD-dominant or CBD + THC) administered for 5 days | Reduction in quantity and frequency of alcohol consumed in CBD group (Percent alcohol use days: CBD vs THC + THC/CBD = 25% vs 34%) |
| Haney et al., 2016 [119] | Randomized, placebo-controlled, cross-over study | Non-treatment seeking, healthy cannabis smokers (n = 31) | 200, 400, 800 mg single-dose CBD (p.o.), or the placebo administered 90 min prior to cannabis administration | No significant reduction in reinforcing (self-administration), physiological (e.g. heart rate), or positive subjective effects (e.g. 'high', 'good effect', 'liking') of smoked cannabis at any doses of CBD |
| Freeman et al., 2020 [120] | Phase 2a, randomized, double-blind, placebo-controlled study | Subjects with cannabis use disorder (n = 48) | 200, 400 or 800 mg CBD (p.o.) or the placebo for 4 weeks during a cessation attempt | 400 and 800 mg CBD decreased THC-COOH:creatinine ratio by 94.21 and 72.02 ng/mL, respectively and increased abstinence from cannabis by 0.48 and 0.27 days per week, respectively |
| Insomnia | ||||
| Monti, 1977 [63] | Animal study | Wistar rats (n = 8) | 20 or 40 mg/kg single-dose CBD (i.p.) | Reduction in slow-wave sleep latency by 16 and 13 min at 20 and 40 mg/kg, respectively. Reduction in wakefulness time and increase in slow-wave sleep time by 39 min at 40 mg/kg |
| Carlini, & Cunha, 1981 [64] | Randomized, double-blind, placebo-controlled, cross-over study | Subjects with insomnia (n = 15) | Single dose of 40, 80, 160 mg CBD (p.o.), nitrazepam 5 mg (p.o.), or placebo administered 30 min before bed | 10 out of 15 subjects experienced longer sleep at 160 mg CBD; Less participants recall their dreams (5–6 out of 15 subjects) at all doses of CBD |
| Shannon et al., 2019 [122] | Retrospective case series | Subjects with sleep (n = 25) or anxiety disorder (n = 47) | 25–175 mg CBD (p.o.) daily for 3 months | 79.2% and 66.7% of patients showed improvement in anxiety and sleep, respectively, in the first month |
| Weight or appetite | ||||
| Ignatowska-Jankowska et al., 2011 [123] | Animal study | Wistar rats (n = 114) | 2.5, 5 mg/kg CBD (i.p.), saline or vehicle daily for 14 days | CBD showed a reduction in body weight gain in rats (weight gain in saline/ vehicle vs CBD at day 14 of treatment: 40 vs 30 g) |
Abbreviations: APP, Amyloid precursor protein; AST, Attentional Switching Task; Aβ, β-amyloid; BACS, Brief Assessment of Cognition in Schizophrenia; BAI, Beck Anxiety Inventory; BDI, Beck Depression Inventory; BL, baseline; BPRS, Brief Psychiatric Rating Scale; CBPI, Canine Brief Pain Inventory; CBT, Cognitive behavioral therapy; CEQ, Cannabis Experiences Questionnaire; CGIC, Caregiver Global Impression of Change; CGI, Clinical Global Impression scale; EPM, elevated plus maze; FNE, Fear of Negative Evaluation Questionnaire; GAF, Global Assessment of Functioning; GFAP, Glial fibrillary acidic proteins; HARS, Hamilton Anxiety Rating Scale; i.a., intraarticular injection; i.p., intraperitoneal injection; i.v., intravenous injection; IL, Interleukin; iNOS; inducible Nitric Oxide Synthase; LSAS, Liebowitz Social Anxiety Scale; MCCB, MATRICS Consensus Cognitive Battery; NORT, Novel object recognition test; NSF, Novelty suppressed feeding; OASIS, Overall Anxiety Severity and Impairment Scale; p.o., oral administration; PANSS, Positive and Negative Syndrome Scale; PDQ, Parkinson’s Disease Questionnaire; PPQ, Parkinson Psychosis Questionnaire; PS1, Presenilin 1; PT, post-treatment; QIDS-A17, Quick Inventory of Depressive Symptoms; RAVLT, Rey Auditory Verbal Learning Test; S/CGIC, Subject/ Caregiver Global Impression of Change; SAD, Social Anxiety Disorder; SCWT, Stroop Color Word; SPSS, State Social Paranoia Scale; SPS, simulated public speaking; SPT, Social preference test; TCQ, Tiffany Craving Scale; TNF-α, Tumor necrosis factor-α; UPDRS, Unified Parkinson’s Disease Rating Scale; VAMS, Visual Analogue Mood Scale; VAS-A, Visual Analogue Scale for Anxiety; VAS-C, Visual Analogue Scale for Craving