The effects of THC on Resting State fMRI.

1. Subject is a legally competent Caucasian male/female from 18 up to and including 45 years old (extremes included) on the day the informed consent is signed.

2. Subject is right-handed.

3. Subject is able to speak, read and understand the local language of the investigational site, is familiar with the procedures of the study, and agrees to participate in the study program by giving oral and written informed consent prior to screening evaluations.

4. Subject is a mild cannabis user for at least one year: cannabis use of no more than once a week, and able to refrain from using cannabinoids from at least 2 weeks prior to the first treatment period to the end of the last study day.

1. Subject has a BMI below 18 or above 28.5 kg/m2.

2. Subject has a significant history of any cardiac or vascular disorder, asthma or other pulmonary disease, major gastrointestinal abnormalities, peptic ulceration, hepatic, neurological, psychiatric, haematological (including bleeding disorders), endocrine, renal, or major genitourinary disease or uses any kind of concomitant medication that - in the opinion of the investigator - may interfere with the study.

3. Subject has a (history of) a significant medical disorder that may pose a risk for the subject or jeopardize the aims of the study, based on medical history, physical examination, ECG and safety laboratory parameters.

4. Subject has a history of clinically significant psychiatric illness in first degree relatives.

5. Subject has a history of hereditary neurological illness in first- or second degree relatives.

6. Female subjects not using the Nuvaring® nor one of the monophasic oral contraceptives (including Diane-35), who are unable and unwilling to also skip the pill/ring-free week, from the screening until the end of the study.

7. Pregnant subjects.

8. Breast feeding subjects.

9. Left-handed handed subjects
10. History of sensitivity / idiosyncrasy to THC, compounds chemically related to these compounds, or excipients which may be employed in the study or to any other drug used in the past.

11. Use of any drug or substance that is known to induce or inhibit drug-metabolizing enzymes within one month prior to the first dose.

12. Use of any drug or substance within one week prior to each dosing, except for paracetamol or some topical medication (i.e. creams, ointments, gels or lotions to induce a local effect without systemic exposure), however, use of such medication have to be reported to the investigator.

13. Subject is currently a regular user (including “recreational uses”) of any illicit drugs, or has (a history of) drug or alcohol abuse (alcohol consumption > 40 grams/day or 4 units/day).

14. Subject smokes more than 5 cigarettes or equivalent per day and/or not able to refrain from smoking on study days.

15. Subject is a habitual and heavy consumer of caffeinated beverages (more than 6 cups of coffee or equivalent/day) at the time of the study and/or is not able to refrain from use of (methyl) xanthines (e.g. coffee, tea, cola, chocolate) from 12 hours prior to dosing until the end of the study day.

16. Unable to refrain from all use of grapefruit and containing products from 2 weeks prior to the first dose until the last study day.

17. Unable to refrain from all use of quinine from 48 hours before dosing until discharge.

18. Unable to refrain from use of alcohol from 48 hours before dosing until discharge, and positive alcohol breath test at screening or admission.

19. Positive urine screen at screening for other drugs than THC, i.e., cocaine, opioids, benzodiazepines, MDMA, methamphetamine and amphetamines.

20. Positive drug test, including THC prior to admission.

21. Positive test result on hepatitis B surface antigen, hepatitis C antibody or HIV antibody test.

22. Unable to refrain from strenuous physical exercise from 24 h prior to each dosing until the end of a study day.

23. Unable to maintain a regular diurnal rhythm.

24. Participation in an investigational drug study within 90 days prior to the first dose and/or participation in more than 4 clinical trials in the last year.

25. Donation of blood/plasma outside limits of Sanquin Blood Supply Foundation guidelines.

26. Subject is provided with a metal medical device like pacemaker, knee or hip prosthesis, ear-implant, vessel-clip, subcutaneous insulin pump, or carries metal particles (e.g. metal splinter in the eye) inside the body.

27. Subject has a significant history of claustrophobia.