Medicinal cannabis has been legal in the UK since 2018 but there is limited information about characteristics of people seeking prescribed cannabis and the effectiveness of this treatment. This paper documents symptom patterns and quality of life among individuals seeking medicinal cannabis and examines changes in symptoms, quality of life and use of pre- scribed opioids using data from an observational registry study of patients (Project Twenty21). Self-report data, including condition-specific symptomatology and general health (quality of life, general health, mood and sleep), were available at treatment entry for 2833 patients seeking medicinal cannabis for any indication and also at 3-month follow-up for 1410 individuals seeking treatment for anxiety disorders, chronic pain or PTSD. Among chronic pain patients, dose and fre- quency of prescribed opioid use was available. There were consistent improvements in disease-specific symptomatology and in general health and quality of life 3 months after commencing treatment. Effect sizes, assessed using Cohen’s d, ranged from 0.50 to 1.17. Among chronic pain patients using opioids at the start of treatment, there was a moderate reduction in Milligrams of Morphine Equivalents: from 22.5 to 8.3mg/day (Cohen’s d=0.29, 95% CI=0.19–0.38). Adverse events were rare (3.2% reported one or more adverse events) and were mostly assessed as either mild or mod- erate severity: the most common AEs were dry mouth (15 occurrences) and feeling drowsy or having red eyes (both reported 11 times). Despite limitations of observational research, including the lack of randomisation or a control group and potential selection bias, these results indicate that prescribed cannabinoids are associated with a reduction in condition-specific symptomatology, improvement in quality of life and a reduction in prescribed opioid use. While fur- ther research is needed to better understand who will most likely benefit from which prescribed cannabinoids, real-world evidence of their effectiveness and safety supports efforts to increase access to these medications.