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Copyright Notice This presentation is copyrighted by the Psychopharmacology Institute. Subscribers can download it and use it for professional use. The contents of the presentation may be modified, but the Psychopharmacology Institute logo must remain visible in all slides.

Phytocannabinoids: Cannabis Plant, Modes of Consumption and Sinsemilla Dr. Paul Morrison Clinical Senior Lecturer Institute of Psychiatry King's College London NHS Consultant Psychiatrist The Maudsley Hospital, London

Possible origins Three subspecies Central Asia Himalayan Mountains Cannabis sativa Cannabis indica Cannabis ruderalis

Δ9-tetrahydrocannabinol (THC) Cannabinoids Δ9-tetrahydrocannabinol (THC) Δ9-tetrahydrocannabivarin (THCV) Cannabidiol (CBD) Cannabinol (CBN) Cannabigerol (CBG) Cannabichromene (CBC) Clarke R. & Watson D. (2007) Cannabis and natural cannabis medicines, in ElSohly MA (ed.) Marijuana and the cannabinoids. Totowa, New Jersey: Humana press Inc. pp. 1-15.

Δ9-tetrahydrocannabinol (THC) Cannabinoids Δ9-tetrahydrocannabinol (THC) Δ9-tetrahydrocannabivarin (THCV) Cannabidiol (CBD) Cannabinol (CBN) Cannabigerol (CBG) Cannabichromene (CBC) Clarke R. & Watson D. (2007) Cannabis and natural cannabis medicines, in ElSohly MA (ed.) Marijuana and the cannabinoids. Totowa, New Jersey: Humana press Inc. pp. 1-15.

THC CBD CBC CBG (Cannabigerol) T allele D allele C allele Clarke R. & Watson D. (2007) Cannabis and natural cannabis medicines, in ElSohly MA (ed.) Marijuana and the cannabinoids. Totowa, New Jersey: Humana press Inc. pp. 1-15.

THC CBD CBC CBG (Cannabigerol) T allele THC dominant plant D allele CBD dominant plant CBC C allele Clarke R. & Watson D. (2007) Cannabis and natural cannabis medicines, in ElSohly MA (ed.) Marijuana and the cannabinoids. Totowa, New Jersey: Humana press Inc. pp. 1-15.

Unpollinated plant (Sinsemilla) Energy: Seed production Pollinated plant Energy Cannabinoid production Sinsemilla: without seeds T allele dominant High THC, no CBD Unpollinated plant (Sinsemilla)

Unpollinated plant (Sinsemilla) Energy: Seed production Pollinated plant Energy: Cannabinoid production Sinsemilla: without seeds T allele dominant High THC, no CBD Unpollinated plant (Sinsemilla)

Unpollinated plant (Sinsemilla) Energy: Seed production Pollinated plant Energy Cannabinoid production Sinsemilla: without seeds T allele dominant High THC, no CBD Unpollinated plant (Sinsemilla)

Unpollinated plant (Sinsemilla) Energy: Seed production Pollinated plant Energy Cannabinoid production Sinsemilla: without seeds T allele dominant High THC, no CBD Unpollinated plant (Sinsemilla)

Modes of consumption

Hash oil: concentrated THC resin Smoked: Rolled cigarette Hash oil: concentrated THC resin Smoked Vaped Ingested orally Food Usually in fat

Hash oil: concentrated THC resin Smoked: Rolled cigarette Hash oil: concentrated THC resin Smoked Vaped Ingested orally Food Usually in fat

Hash oil: concentrated THC resin Smoked: Rolled cigarette Hash oil: concentrated THC resin Smoked Vaped Ingested orally Food Usually in fat

Sinsemilla

Intense cultivation methods, strains selectively bred High in THC : Sinsemilla Intense cultivation methods, strains selectively bred High in THC : No cannabidiol (CBD) Unbalanced product Traditional cannabis 4-5% THC Cannabidiol (CBD) Potter DJ. et al (2008) Potency of delta-9-THC and other cannabinoids in cannabis in England in 2005: implications for psychoactivity and pharmacology. Journal of forensic sciences. 53, 90-94.

Intense cultivation methods, strains selectively bred Sinsemilla Intense cultivation methods, strains selectively bred High in THC : > 15% No cannabidiol (CBD) Unbalanced product Traditional cannabis 4-5% THC Cannabidiol (CBD) Potter DJ. et al (2008) Potency of delta-9-THC and other cannabinoids in cannabis in England in 2005: implications for psychoactivity and pharmacology. Journal of forensic sciences. 53, 90-94.

Intense cultivation methods, strains selectively bred Sinsemilla Intense cultivation methods, strains selectively bred High in THC : > 15% No cannabidiol (CBD) Unbalanced product Traditional cannabis 4-5% THC Cannabidiol (CBD) Potter DJ. et al (2008) Potency of delta-9-THC and other cannabinoids in cannabis in England in 2005: implications for psychoactivity and pharmacology. Journal of forensic sciences. 53, 90-94.

Intense cultivation methods, strains selectively bred Sinsemilla Intense cultivation methods, strains selectively bred High in THC : > 15% No cannabidiol (CBD) Unbalanced product Traditional cannabis 4-5% THC Cannabidiol (CBD) Potter DJ. et al (2008) Potency of delta-9-THC and other cannabinoids in cannabis in England in 2005: implications for psychoactivity and pharmacology. Journal of forensic sciences. 53, 90-94.

THC CBD Could be inhibited by: CB1 Animal models Effects

THC CBD CB1 Effects Could be inhibited by: Sinsemilla hazards: Animal models Sinsemilla hazards: Attributable to CBD absence? Effects

Could CBD counteract THC at the psychological level? Healthy volunteers Session 1: CBD+THC Session 2: THC+ placebo THC could increase psychosis scores and worsen memory performance CBD: protected against THC effects Lower psychosis scores Counteracted memory effects Englund A, Morrison PD, Nottage J, Hague D, Kane F, Bonaccorso S, et al. Cannabidiol inhibits THC-elicited paranoid symptoms and hippocampal-dependent memory impairment. Journal of psychopharmacology 2013;27(1):19-27.

Could CBD counteract THC at the psychological level? Healthy volunteers Session 1: CBD+THC Session 2: THC+ placebo THC could increase psychosis scores and worsen memory performance CBD: protected against THC effects Lower psychosis scores Counteracted memory effects Englund A, Morrison PD, Nottage J, Hague D, Kane F, Bonaccorso S, et al. Cannabidiol inhibits THC-elicited paranoid symptoms and hippocampal-dependent memory impairment. Journal of psychopharmacology 2013;27(1):19-27.

Could CBD counteract THC at the psychological level? Healthy volunteers Session 1: CBD+THC Session 2: THC+ placebo THC could increase psychosis scores and worsen memory performance CBD: protected against THC effects Lower psychosis scores Counteracted memory effects Englund A, Morrison PD, Nottage J, Hague D, Kane F, Bonaccorso S, et al. Cannabidiol inhibits THC-elicited paranoid symptoms and hippocampal-dependent memory impairment. Journal of psychopharmacology 2013;27(1):19-27.

Could CBD counteract THC at the psychological level? Healthy volunteers Session 1: CBD+THC Session 2: THC+ placebo THC could increase psychosis scores and worsen memory performance CBD: protected against THC effects Lower psychosis scores Counteracted memory effects Englund A, Morrison PD, Nottage J, Hague D, Kane F, Bonaccorso S, et al. Cannabidiol inhibits THC-elicited paranoid symptoms and hippocampal-dependent memory impairment. Journal of psychopharmacology 2013;27(1):19-27.

Could CBD counteract THC at the psychological level? Healthy volunteers Session 1: CBD+THC Session 2: THC+ placebo THC could increase psychosis scores and worsen memory performance CBD: protected against THC effects Lower psychosis scores CBD counteracted memory effects Englund A, Morrison PD, Nottage J, Hague D, Kane F, Bonaccorso S, et al. Cannabidiol inhibits THC-elicited paranoid symptoms and hippocampal-dependent memory impairment. Journal of psychopharmacology 2013;27(1):19-27.

Appears to soften THC effects CBD

First-episode psychosis patients vs healthy controls High potency cannabis: 5x more likely to suffer a psychotic disorder Hashish use: not related to increased risk of psychosis Lower THC content, presence of CBD Sinsemilla Highest risk of psychotic disorder South London: ¼ of new cases of psychotic illness Di Forti, M., Marconi, A., Carra, E., Fraietta, S., Trotta, A., Bonomo, M., ... & Stilo, S. A. (2015). Proportion of patients in south London with first-episode psychosis attributable to use of high potency cannabis: a case-control study. The Lancet Psychiatry, 2(3), 233-238.

First-episode psychosis patients vs healthy controls High potency cannabis: 5x more likely to suffer a psychotic disorder Hashish use: not related to increased risk of psychosis Lower THC content, presence of CBD Sinsemilla Highest risk of psychotic disorder South London: ¼ of new cases of psychotic illness Di Forti, M., Marconi, A., Carra, E., Fraietta, S., Trotta, A., Bonomo, M., ... & Stilo, S. A. (2015). Proportion of patients in south London with first-episode psychosis attributable to use of high potency cannabis: a case-control study. The Lancet Psychiatry, 2(3), 233-238.

First-episode psychosis patients vs healthy controls High potency cannabis: 5x more likely to suffer a psychotic disorder Hashish use: not related to increased risk of psychosis Lower THC content, presence of CBD Sinsemilla Highest risk of psychotic disorder South London: ¼ of new cases of psychotic illness Di Forti, M., Marconi, A., Carra, E., Fraietta, S., Trotta, A., Bonomo, M., ... & Stilo, S. A. (2015). Proportion of patients in south London with first-episode psychosis attributable to use of high potency cannabis: a case-control study. The Lancet Psychiatry, 2(3), 233-238.

First-episode psychosis patients vs healthy controls High potency cannabis: 5x more likely to suffer a psychotic disorder Hashish use: not related to increased risk of psychosis Lower THC content, presence of CBD Sinsemilla Highest risk of psychotic disorder South London: ¼ of new cases of psychotic illness Di Forti, M., Marconi, A., Carra, E., Fraietta, S., Trotta, A., Bonomo, M., ... & Stilo, S. A. (2015). Proportion of patients in south London with first-episode psychosis attributable to use of high potency cannabis: a case-control study. The Lancet Psychiatry, 2(3), 233-238.

First-episode psychosis patients vs healthy controls High potency cannabis: 5x more likely to suffer a psychotic disorder Hashish use: not related to increased risk of psychosis Lower THC content, presence of CBD Sinsemilla Highest risk of psychotic disorder South London: ¼ of new cases of psychotic illness Di Forti, M., Marconi, A., Carra, E., Fraietta, S., Trotta, A., Bonomo, M., ... & Stilo, S. A. (2015). Proportion of patients in south London with first-episode psychosis attributable to use of high potency cannabis: a case-control study. The Lancet Psychiatry, 2(3), 233-238.

Key Points Cannabis is subdivided into three species: C. sativa, C. indica, C. ruderalis Each species has differences in cannabinoid concentrations Sinsemilla is a very potent product. It is high in THC and has no CBD CBD appears to soften the effects of THC Sinsemilla use is associated to higher risk of psychosis than hashish THC

Key Points Cannabis is subdivided into three species: C. sativa, C. indica, C. ruderalis Each species has differences in cannabinoid concentrations Sinsemilla is a very potent product. It is high in THC and has no CBD CBD appears to soften the effects of THC Sinsemilla use is associated to higher risk of psychosis than hashish THC

Next Presentation: Cannabinoid Pharmacology and Synthetic Cannabinoids