Cannabis and its analogues are regarded as having a relatively positive safety profile, with mild adverse events commonly including headache, dry eyes, dry mouth, dizziness, light-headedness, numbness, and cough. Serious adverse effects are rare with cannabis or its constituents. Cannabis has low to moderate dependence potential and the active dose is very far below the lethal dose. THC has been associated with a number of side effects including anxiety, cholinergic deficits, and immunosuppression. THC can produce psychoactive effects that may not be well tolerated in some patients. Patients who are less experienced with cannabis tend to demonstrate more frequent side effects. Cannabinoids often work best in conjunction with other cannabinoids. For example, CBD can mitigate the psychoactive effects of THC. Increases in plasma cortisol due to administered THC have been demonstrated and increases in heart rate, and both transient hypotension and increased systolic blood pressure have also been recorded. A recent review found that CBD is non-toxic to non-transformed cells and does not affect appetite or various physiologic or psychologic functions. Additionally, it found that chronic use and doses up to 1,500 mg/day were reportedly well tolerated in humans. However, CBD was found to potentially affect hepatic drug metabolism and possibly decrease fertilization capacity. In a study involving a pure CBD extract, the most common side-effects experienced were somnolence, decreased appetite, diarrhea, fatigue and convulsion.