There is only one report of a clinical study of Δ9-THC to treat cancerReference 1334. Intra-tumoural administration of Δ9-THC appeared to be well tolerated and the effect of Δ9-THC on patient survival was similar to that observed in other studies using chemotherapeutic agents such as temozolomide or carmustineReference 1335Reference 1336. In addition, results from a separate in vitro study suggest that CBD enhanced the inhibitory effects of Δ9-THC on human glioblastoma cell proliferation and survivalReference 1338.
No differences were noted between THC and diazepam in VAS measures of alertness, mood, and calmness but THC was associated with a significant increase in anxiety compared to diazepam. Most frequent adverse events associated with THC were somnolence, dry mouth, dizziness and euphoric mood.
Two studies that analyzed cannabinoid levels in hair samples from 140 individuals found that those who had only THC in their hair exhibited greater positive symptoms with higher levels of hallucinations and delusions than those with both THC and CBD in their hair and those with no cannabinoidsReference 1131Reference 1132. Adolescence is also the period of time where the brain’s ECS undergoes dynamic changes including a spike in mRNA levels of the CB1 receptor, a steady increase in the level of anandamide, and a more pronounced decrease in the levels of 2-AGReference 539. The ECS is implicated in the myelination of various tracts and in neuroplasticity and synaptic functionReference 539. It is therefore conceivable that exogenously applied cannabinoids such as THC can perturb the fine balance of endocannabinoid levels and the proper functioning of the CB1 receptor resulting in a change in course of neurodevelopment during this period. In one case-control study with 280 people with a first episode of psychosis and 174 controls, patients reported using higher-potency cannabis containing high THC and low CBD compared to the controls who reported using cannabis containing equal amounts of THC and CBDReference 1112.
One caveat to this is that in animal models it appears that pre-treatment with CBD 15 to 60 min prior to administration of THC, but not co-administration, is associated with increased blood and intracerebral levels of THC and THC-associated immobilityReference 123Reference 131. Furthermore, a higher ratio of CBD to THC also appears important in attenuating the psychoactive effects of THCReference 135Reference 1108Reference 1135.
Pharmacokinetic parameters of THC were similar between opioid and non-opioid users and showed a delayed absorption and increased variability compared to healthy volunteers. Study limitations included small number of study subjects, short trial duration, single dose design, and low dosage of THC. Findings from a cross-sectional survey of 291 patients with IBD (Crohn’s disease or ulcerative colitis) suggested that the vast majority of those patients reported using cannabis to relieve abdominal pain and to improve appetiteReference 185. In contrast to patients with Crohn’s disease, a greater proportion of patients with ulcerative colitis reported using cannabis to improve diarrheal symptoms. In general, patients reported being more likely to use cannabis for symptom relief if they had a history of abdominal surgery, chronic analgesic use, alternative/complementary medicine use, and a lower SIBDQ (short IBD questionnaire) score.
Both ulcerative colitis and Crohn’s disease patients reported using cannabis to improve stress levels and sleep. The majority of cannabis users reported using once per month or less, but 16% reported using cannabis daily or several times per day. The vast majority (77%) of users reported smoking cannabis as a joint without tobacco, 18% of users smoked it with tobacco, 3% used a water pipe, and 1% reported oral ingestion. Approximately one-third of patients in this study reported significant side effects associated with the use of cannabis such as paranoia, anxiety, and palpitations. Other commonly reported side effects included feeling "high", dry mouth, drowsiness, memory loss, hallucinations, and depression.
The study revealed that most of the survey participants reported smoking cannabis while fewer reported ingestion, vapourization, and use of homemade concentrated oil. The majority of the patients reported using cannabis daily or more frequently.
While no serious adverse effects were noted, there were increases in the incidence of somnolence, dizziness, euphoric mood, lethargy, anxiety, dysgeusia, and headache. No significant effects on plasma levels of THC, CBD or 11-hydroxy-THC were noted with omeprazole.
Complementing these findings, an in vivo study showed that combined treatment with Δ9-THC (15 mg/kg/day) and temozolomide (5 mg/kg/day) reduced the growth of glioma tumour xenografts in mice in a synergistic mannerReference 1331. These studies suggest that cannabinoids might sensitize certain tumours to the anti-neoplastic action of conventional chemotherapeutic drugs. The study reported a lack of efficacy with THC in reducing chronic pain associated with chronic pancreatitis but good tolerance with only mild or moderate adverse events.
Cannabis was reported to provide benefit in altered sense, weight maintenance, depression, pain, appetite, dysphagia, xerostomia, muscle spasms, and sticky saliva as side effects of best hemp oil radiotherapy. Pre-clinical in vitro and in vivo studies investigating the effects of combining cannabinoids with frequently used chemotherapeutic agents have also been performed. One in vitro study showed that combining sub-maximal doses of Δ9-THC (0.75 μM) with cisplatin or doxorubicin reduced the viability of an astrocytoma cell line in a synergistic mannerReference 1330. Likewise, combining sub-maximal doses of Δ9-THC with temozolomide reduced the in vitro viability of several human glioma cell lines and primary cultures of glioma cells derived from human glioblastoma multiforme biopsiesReference 1331.