Endocannabinoids, cannabinoids and...

70
1 Endocannabinoids, cannabinoids and cannabis Celia Morgan University of Exeter

Transcript of Endocannabinoids, cannabinoids and...

  • 1

    Endocannabinoids, cannabinoids and cannabis

    Celia Morgan

    University of Exeter

  • 2

    Cannabis

  • 3

    Cannabis

  • 4

    Cannabis

  • 5

    Cannabis

    • Trichomes on cannabis

    plant • Evolved to protect the

    plant • Contain chemicals:

    ‘cannabinoids’

  • 6

    Cannabinoids > 80 different cannabinoids Δ9-tetrahydrocannabinol

    (THC) induces anxiety, memory impairment, ‘stoned’ and schizophrenia-like effects (D’Souza et al, 2004; 2008).

    Cannabidiol (CBD) anxiolytic, reduces paranoia, neuroprotective (Zuardi et al. 2006; Hermann et al. 2007; Leweke et al, 2007).

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    • Different types of cannabis vary in levels of cannabinoids

    Afghani - BC bud – big bud – bomb – Blue velvet – boo-yah – bubble – bud – buddha – burger – Charis – chiba – chino – choke – cigga-weed – cigweed – combustible herbage – crippy – dank - dirt weed – ditch weed – doja – doob – dope – drat – draw – dro – dub – dube – Dutchie – endo – erve – gange – ganja – giggle stick – gonj – grass – green – green bud – hash - heim – herb – herbal refreshment – Holland’s Hope – hog leg – hooter – hydro – indica – indo – jib –– keef – kief – Kush – Mary Jane – Mexican dirt weed – MJ – Mr. J – Nepalese - Northern Lights – paca lolo – Purple Haze – pot – purp –– Lebanese red - reggie – schwag –silver weed – skunk – smoke – soapbar tea – Thai stick – treats – tweed – wacky baccy – vortex - weed – White Widow - woolies – zombie

    http://images.google.co.uk/imgres?imgurl=http://a.abcnews.com/images/Health/apg_marijuana_070727_ms.jpg&imgrefurl=http://abcnews.go.com/Health/CancerPreventionAndTreatment/wireStory?id=4207595&h=310&w=413&sz=18&hl=en&start=45&tbnid=1jTDEG1rK3BSLM:&tbnh=94&tbnw=125&prev=/images?q=cannabis&start=36&gbv=2&ndsp=18&hl=en&sa=N

  • 8

    Levels of THC and CBD in 3000 cannabis seizures UK

    King and Hardwick, 2008

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    Increasing THC potency in UK cannabis seizures

    12.13

    2011

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    Cannabis samples collected, n=422

    Chart2

    skunk

    herbal

    resin / hashish

    70

    10

    13

    Sheet1

    skunkherbalresin / hashish

    Recreational users4137

    Daily users2976

    Group * skunk herbal hash Crosstabulation

    skunk herbal hashTotal

    skunkherbalresin / hashish

    Grouprecreational userCount413751skunkherbalresin / hashish

    % within Group80.39215686275.882352941213.7254901961100701013

    % within skunk herbal hash58.57142857143053.846153846254.8387096774

    % of Total44.08602150543.22580645167.526881720454.8387096774

    daily userCount297642

    % within Group69.047619047616.666666666714.2857142857100

    % within skunk herbal hash41.42857142867046.153846153845.1612903226

    % of Total31.18279569897.52688172046.451612903245.1612903226

    TotalCount70101393

    % within Group75.268817204310.75268817213.9784946237100

    % within skunk herbal hash100100100100

    % of Total75.268817204310.75268817213.9784946237100

    Sheet1

    Sheet2

    Sheet3

  • 11

    n = 371

    CBD and THC levels

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    n = 371 CBD levels

    are declining: why?

    CBD and THC levels

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    Preferences for types of cannabis in 16-23 year olds

    Chart1

    no preference

    Resin/ hash

    Low potency herbal

    Skunk

    28

    21

    26

    39

    Sheet1

    Do you have a preference for a type of cannabis

    Frequency

    Validno preference28

    Resin/ hash21

    Low potency herbal26

    Skunk39

    Sheet1

    Sheet2

    Sheet3

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    Where has the CBD gone?

    • Potter (2010) • Majority of UK consumed

    cannabis now grown intensively in illegal ‘farms’

    • Intensive heating decreases levels of CBD in trichomes

    • Hashish combines a variety of cannabis plants – Most cannabis seeds in UK

    now are a variety with no CBD

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    Skunk and cannabis use disorder • Cannabis second only to heroin as reason for presentation at drug services

    across EU – 25% cases (EMCDDA, 2014)

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    ‘Skunk’ use linked to psychosis

    Di Forti et al., 2015, Lancet Psychiatry

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    Research question • Given that levels of cannabinoids vary in different cannabis

    preparations • THC and CBD have opposing effects in the laboratory • Skunk use is more prevalent in psychosis and cannabis use

    disorder

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    Research question • Given that levels of cannabinoids vary in different cannabis

    preparations • THC and CBD have opposing effects in the laboratory • Skunk use is more prevalent in psychosis and cannabis use

    disorder Does CBD protect against the harmful effects of THC in cannabis users?

  • 19

    • Study 1: Cannabinoids in hair • Study 2: Naturally occurring cannabinoids in

    hair and cannabis

  • 20

    Looking at cannabinoids in the hair…

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    Looking at cannabinoids in the hair…

    ~ 3 years

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    Study 1: THC/CBD in hair

    • Hair analysis • 3cm hair samples ~ 3 months • 132 people, mean age 27 years

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    Psychotic-like experiences: O-LIFE – Unusual Experiences ~ Paranoia, Illusions & Delusions

    • When you look in the mirror does your face sometimes seem quite different from usual?

    • Do think you could learn to read others minds if you wanted to? • Do you sometimes think people are laughing about you behind your

    back?

    THC only n=20

    CBD and THC n=26

    Neither n=86

    Study 1: THC/CBD in hair

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    **

    Study 1: THC/CBD in hair

    THC/CBD in hair

    Morgan & Curran, 2008 British Journal of Psychiatry

    Chart1

    Unusual ExperiencesUnusual ExperiencesUnusual Experiences

    No Cannabis

    THC only

    THC + CBD

    OLIFE Score

    3.5

    6.8

    4.05

    Sheet1

    Unusual ExperiencesCognitive DisorganisationIntrovertive AnhedoniaImpulsive Non-conformity0.50.30.20.2

    No Cannabis3.54.95.55.20.750.40.40.4

    THC only6.85.35.35.350.50.50.30.3

    THC + CBD4.055.14.35.3

    Sheet1

    0.50.750.5

    0.30.40.5

    0.20.40.3

    0.20.40.3

    No Cannabis

    THC only

    THC + CBD

    Sheet2

    Sheet3

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    THC / CBD

    • Cannabis users with THC only in hair experience higher levels of unusual experiences than THC+CBD

    Interpretations:

    - Pre-existing group differences? - Is CBD protective against psychotic-like effects of THC?

    Study 1: THC/CBD in hair

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    Study 2: Naturalistic study of the effects of cannabinoids

    • n=626 individuals; 16-23 year olds • Tested in own home, smoking own supply of cannabis • Tested cannabis smoked for CBD and THC • Looked at hair for chronic use

    Sober

    Stoned

    Stoned

    Sober Day 0

    Day 7

  • 27

    *

    Same amount of THC; differed in CBD

    Acute effects: memory

    Morgan et al. (2010) British Journal of Psychiatry

    Study 2: Naturalistic study of cannabinoids

    Chart1

    IntoxicatedIntoxicated

    Not intoxicatedNot intoxicated

    Low CBD:THC

    High CBD:THC

    Delayed prose recall

    4.7813

    6.8103

    6.25

    6.569

    Verbal fluency

    IntoxicatedNot intoxicated

    Low CBD:THC16.062513.8125

    High CBD:THC16.103416.6207

    Standard Error for intoxicatedStandard error for Non intoxicated verbal fluency

    Low CBD:THC1.00996768660.9195870656

    High CBD:THC0.83540061650.8226097992

    Verbal fluency

    1.00996768660.8354006165

    0.91958706560.8226097992

    Low CBD:THC

    High CBD:THC

    Verbal fluency

    Category fluency

    IntoxicatedNot intoxicated

    Low CBD:THC16.718816.75

    High CBD:THC19.620718.4138

    Standard Error for intoxicatedStandard error for Non intoxicated verbal fluency

    Low CBD:THC0.65259238390.8364189338

    High CBD:THC0.92103773560.8545978006

    Category fluency

    0.65259238390.9210377356

    0.83641893380.8545978006

    Low CBD:THC

    High CBD:THC

    Category fluency

    Prose delayed

    IntoxicatedNot intoxicated

    Low CBD:THC4.78136.25

    High CBD:THC6.81036.569

    Standard Error for intoxicatedStandard error for Non intoxicated verbal fluency

    Low CBD:THC0.50097631560.7010221273

    High CBD:THC0.72491374730.5849737404

    Prose delayed

    0.50097631560.7249137473

    0.70102212730.5849737404

    Low CBD:THC

    High CBD:THC

    Prose delayed

    PSI

    IntoxicatedNot intoxicated

    Low CBD:THC26.387116.4194

    High CBD:THC29.545518.7727

    Standard Error for intoxicatedStandard error for Non intoxicated verbal fluency

    Low CBD:THC2.7861703531.5792837891

    High CBD:THC3.7107115643.5547253919

    PSI

    2.7861703533.710711564

    1.57928378913.5547253919

    Low CBD:THC

    High CBD:THC

    PSI

    Stoned rating

    IntoxicatedNot Intoxicated

    Low CBD:THC6.6251.3438

    High CBD:THC6.44831.3448

    Standard Error for intoxicatedStandard error for Non intoxicated verbal fluency

    Low CBD:THC0.24842075440.3528392127

    High CBD:THC0.20022042750.359892421

    Stoned rating

    0.24842075440.2002204275

    0.35283921270.359892421

    Low CBD:THC

    High CBD:THC

    Stoned data (cm)

    line graph

    FoodNeutralDrug

    Low CBD:THC0.95410.14030.9081

    High CBD:THC0.6950.03080.265

    SE-FoodSE- NeutralSE -Drug

    Low CBD:THC0.09256857270.12773349470.0939605138

    High CBD:THC0.12986136690.10211009070.1498495888

    line graph

    0.09256857270.09256857270.12986136690.1298613669

    0.12773349470.12773349470.10211009070.1021100907

    0.09396051380.09396051380.14984958880.1498495888

    Low CBD:THC

    High CBD:THC

    Pleasantness Rating

  • 28

    *

    Same amount of THC; differed in CBD

    Acute effects: memory

    Morgan et al. (2010) British Journal of Psychiatry

    Chart1

    IntoxicatedIntoxicated

    Not intoxicatedNot intoxicated

    Low CBD:THC

    High CBD:THC

    Delayed prose recall

    4.7813

    6.8103

    6.25

    6.569

    Verbal fluency

    IntoxicatedNot intoxicated

    Low CBD:THC16.062513.8125

    High CBD:THC16.103416.6207

    Standard Error for intoxicatedStandard error for Non intoxicated verbal fluency

    Low CBD:THC1.00996768660.9195870656

    High CBD:THC0.83540061650.8226097992

    Verbal fluency

    1.00996768660.8354006165

    0.91958706560.8226097992

    Low CBD:THC

    High CBD:THC

    Verbal fluency

    Category fluency

    IntoxicatedNot intoxicated

    Low CBD:THC16.718816.75

    High CBD:THC19.620718.4138

    Standard Error for intoxicatedStandard error for Non intoxicated verbal fluency

    Low CBD:THC0.65259238390.8364189338

    High CBD:THC0.92103773560.8545978006

    Category fluency

    0.65259238390.9210377356

    0.83641893380.8545978006

    Low CBD:THC

    High CBD:THC

    Category fluency

    Prose delayed

    IntoxicatedNot intoxicated

    Low CBD:THC4.78136.25

    High CBD:THC6.81036.569

    Standard Error for intoxicatedStandard error for Non intoxicated verbal fluency

    Low CBD:THC0.50097631560.7010221273

    High CBD:THC0.72491374730.5849737404

    Prose delayed

    0.50097631560.7249137473

    0.70102212730.5849737404

    Low CBD:THC

    High CBD:THC

    Prose delayed

    PSI

    IntoxicatedNot intoxicated

    Low CBD:THC26.387116.4194

    High CBD:THC29.545518.7727

    Standard Error for intoxicatedStandard error for Non intoxicated verbal fluency

    Low CBD:THC2.7861703531.5792837891

    High CBD:THC3.7107115643.5547253919

    PSI

    2.7861703533.710711564

    1.57928378913.5547253919

    Low CBD:THC

    High CBD:THC

    PSI

    Stoned rating

    IntoxicatedNot Intoxicated

    Low CBD:THC6.6251.3438

    High CBD:THC6.44831.3448

    Standard Error for intoxicatedStandard error for Non intoxicated verbal fluency

    Low CBD:THC0.24842075440.3528392127

    High CBD:THC0.20022042750.359892421

    Stoned rating

    0.24842075440.2002204275

    0.35283921270.359892421

    Low CBD:THC

    High CBD:THC

    Stoned data (cm)

    line graph

    FoodNeutralDrug

    Low CBD:THC0.95410.14030.9081

    High CBD:THC0.6950.03080.265

    SE-FoodSE- NeutralSE -Drug

    Low CBD:THC0.09256857270.12773349470.0939605138

    High CBD:THC0.12986136690.10211009070.1498495888

    line graph

    0.09256857270.09256857270.12986136690.1298613669

    0.12773349470.12773349470.10211009070.1021100907

    0.09396051380.09396051380.14984958880.1498495888

    Low CBD:THC

    High CBD:THC

    Pleasantness Rating

  • 29

    Attentional Bias

    • Cues associated with drug use (e.g. cannabis, pipe, joint) grab the users’ attention

    • Increases drug craving and predicts relapse

  • 30

    * *

  • 31

    * *

  • 32

    Exposure: 250ms or 2000ms

  • 33

    * *

  • 34

  • 35

    * *

  • 36

  • 37

    -60-40-20

    020406080

    100120

    Food Drug

    Not Intoxicated

    Atte

    ntio

    nal b

    ias

    (ms)

    Low CBD:THCHigh CBD:THC

    Stimulus exposure = 250ms Morgan, Freeman, Schafer & Curran (2010)

    Neuropsychopharmacology

    Dependence Attentional Bias Study 2: Naturalistic study of cannabinoids

    Chart1

    13.940997281418.7402758438

    18.643240227115.4756500478

    Food Not IntoxicatedFood Not Intoxicated17.790069469718.3150511554

    DrugDrug10.915995321710.5135063612

    Low CBD:THC

    High CBD:THC

    Attentional bias (ms)

    -0.5267383226

    12.595

    83.0123655806

    88.1788386333

    Verbal fluency

    IntoxicatedNot intoxicated

    Low CBD:THC16.062513.8125

    High CBD:THC16.103416.6207

    Standard Error for intoxicatedStandard error for Non intoxicated verbal fluency

    Low CBD:THC1.00996768660.9195870656

    High CBD:THC0.83540061650.8226097992

    Verbal fluency

    1.00996768660.8354006165

    0.91958706560.8226097992

    Low CBD:THC

    High CBD:THC

    Verbal fluency

    Category fluency

    IntoxicatedNot intoxicated

    Low CBD:THC16.718816.75

    High CBD:THC19.620718.4138

    Standard Error for intoxicatedStandard error for Non intoxicated verbal fluency

    Low CBD:THC0.65259238390.8364189338

    High CBD:THC0.92103773560.8545978006

    Category fluency

    0.65259238390.9210377356

    0.83641893380.8545978006

    Low CBD:THC

    High CBD:THC

    Category fluency

    Not intoxicated only_prose dela

    Not intoxicated

    Low CBD:THC6.25

    High CBD:THC6.569

    Standard Error for intoxicatedStandard error for Non intoxicated verbal fluency

    Low CBD:THC0.50097631560.7010221273

    High CBD:THC0.72491374730.5849737404

    Not intoxicated only_prose dela

    0.70102212730.5849737404

    Low CBD:THC

    High CBD:THC

    Prose delayed

    Prose delayed

    IntoxicatedNot intoxicated

    Low CBD:THC4.78136.25

    High CBD:THC6.81036.569

    Standard Error for intoxicatedStandard error for Non intoxicated verbal fluency

    Low CBD:THC0.50097631560.7010221273

    High CBD:THC0.72491374730.5849737404

    Prose delayed

    0.50097631560.7249137473

    0.70102212730.5849737404

    Low CBD:THC

    High CBD:THC

    Prose delayed

    PSI

    IntoxicatedNot intoxicated

    Low CBD:THC26.387116.4194

    High CBD:THC29.545518.7727

    Standard Error for intoxicatedStandard error for Non intoxicated verbal fluency

    Low CBD:THC2.7861703531.5792837891

    High CBD:THC3.7107115643.5547253919

    PSI

    2.7861703533.710711564

    1.57928378913.5547253919

    Low CBD:THC

    High CBD:THC

    PSI

    Stoned rating

    IntoxicatedNot Intoxicated

    Low CBD:THC6.6251.3438

    High CBD:THC6.44831.3448

    Standard Error for intoxicatedStandard error for Non intoxicated verbal fluency

    Low CBD:THC0.24842075440.3528392127

    High CBD:THC0.20022042750.359892421

    Stoned rating

    0.24842075440.2002204275

    0.35283921270.359892421

    Low CBD:THC

    High CBD:THC

    Stoned data (cm)

    line graph

    FoodNeutralDrug

    Low CBD:THC0.95410.14030.9081

    High CBD:THC0.6950.03080.265

    SE-FoodSE- NeutralSE -Drug

    Low CBD:THC0.09256857270.12773349470.0939605138

    High CBD:THC0.12986136690.10211009070.1498495888

    line graph

    0.09256857270.09256857270.12986136690.1298613669

    0.12773349470.12773349470.10211009070.1021100907

    0.09396051380.09396051380.14984958880.1498495888

    Low CBD:THC

    High CBD:THC

    Rating

    attentional bias not intoxicatd

    Mean

    Descriptives

    Not IntoxicatedStd. Error

    FoodDrug

    Low CBD:THC-0.526738322683.012365580613.940997281418.643240227117.790069469710.9159953217

    High CBD:THC12.59588.178838633318.740275843815.475650047818.315051155410.5135063612

    Drug_intoxicated1

    2

    Drug Non_intoxicated1

    2

    Food Non-intoxicated1

    2

    attentional bias not intoxicatd

    13.940997281418.7402758438

    18.643240227115.4756500478

    17.790069469718.3150511554

    10.915995321710.5135063612

    Low CBD:THC

    High CBD:THC

    Bias (ms)

    Attentional bias both

    IntoxicatedNot IntoxicatedStd. Error

    FoodDrugFoodDrug

    Low CBD:THC40.139652812529.0633804688-0.526738322683.012365580613.940997281418.643240227117.790069469710.9159953217

    High CBD:THC-9.080355875-45.773671843812.59588.178838633318.740275843815.475650047818.315051155410.5135063612

    Attentional bias both

    13.940997281418.7402758438

    18.643240227115.4756500478

    17.790069469718.3150511554

    10.915995321710.5135063612

    Low CBD:THC

    High CBD:THC

    Bias (ms)

  • 38

    -60-40-20

    020406080

    100120

    Food Drug Food Drug

    Intoxicated Not Intoxicated

    Atte

    ntio

    nal B

    ias

    (ms)

    Low CBD:THCHigh CBD:THC

    Morgan, Freeman, Schafer & Curran (2010) Neuropsychopharmacology

    * *

    Dependence Attentional Bias

    Study 2: Naturalistic study of cannabinoids

    Chart2

    Food IntoxicatedFood Intoxicated13.940997281418.7402758438

    DrugDrug18.643240227115.4756500478

    Food Not IntoxicatedFood Not Intoxicated17.790069469718.3150511554

    DrugDrug10.915995321710.5135063612

    Low CBD:THC

    High CBD:THC

    Attentional Bias (ms)

    40.1396528125

    -9.080355875

    29.0633804688

    -45.7736718438

    -0.5267383226

    12.595

    83.0123655806

    88.1788386333

    Verbal fluency

    IntoxicatedNot intoxicated

    Low CBD:THC16.062513.8125

    High CBD:THC16.103416.6207

    Standard Error for intoxicatedStandard error for Non intoxicated verbal fluency

    Low CBD:THC1.00996768660.9195870656

    High CBD:THC0.83540061650.8226097992

    Verbal fluency

    1.00996768660.8354006165

    0.91958706560.8226097992

    Low CBD:THC

    High CBD:THC

    Verbal fluency

    Category fluency

    IntoxicatedNot intoxicated

    Low CBD:THC16.718816.75

    High CBD:THC19.620718.4138

    Standard Error for intoxicatedStandard error for Non intoxicated verbal fluency

    Low CBD:THC0.65259238390.8364189338

    High CBD:THC0.92103773560.8545978006

    Category fluency

    0.65259238390.9210377356

    0.83641893380.8545978006

    Low CBD:THC

    High CBD:THC

    Category fluency

    Not intoxicated only_prose dela

    Not intoxicated

    Low CBD:THC6.25

    High CBD:THC6.569

    Standard Error for intoxicatedStandard error for Non intoxicated verbal fluency

    Low CBD:THC0.50097631560.7010221273

    High CBD:THC0.72491374730.5849737404

    Not intoxicated only_prose dela

    0.70102212730.5849737404

    Low CBD:THC

    High CBD:THC

    Prose delayed

    Prose delayed

    IntoxicatedNot intoxicated

    Low CBD:THC4.78136.25

    High CBD:THC6.81036.569

    Standard Error for intoxicatedStandard error for Non intoxicated verbal fluency

    Low CBD:THC0.50097631560.7010221273

    High CBD:THC0.72491374730.5849737404

    Prose delayed

    0.50097631560.7249137473

    0.70102212730.5849737404

    Low CBD:THC

    High CBD:THC

    Prose delayed

    PSI

    IntoxicatedNot intoxicated

    Low CBD:THC26.387116.4194

    High CBD:THC29.545518.7727

    Standard Error for intoxicatedStandard error for Non intoxicated verbal fluency

    Low CBD:THC2.7861703531.5792837891

    High CBD:THC3.7107115643.5547253919

    PSI

    2.7861703533.710711564

    1.57928378913.5547253919

    Low CBD:THC

    High CBD:THC

    PSI

    Stoned rating

    IntoxicatedNot Intoxicated

    Low CBD:THC6.6251.3438

    High CBD:THC6.44831.3448

    Standard Error for intoxicatedStandard error for Non intoxicated verbal fluency

    Low CBD:THC0.24842075440.3528392127

    High CBD:THC0.20022042750.359892421

    Stoned rating

    0.24842075440.2002204275

    0.35283921270.359892421

    Low CBD:THC

    High CBD:THC

    Stoned data (cm)

    line graph

    FoodNeutralDrug

    Low CBD:THC0.95410.14030.9081

    High CBD:THC0.6950.03080.265

    SE-FoodSE- NeutralSE -Drug

    Low CBD:THC0.09256857270.12773349470.0939605138

    High CBD:THC0.12986136690.10211009070.1498495888

    line graph

    0.09256857270.09256857270.12986136690.1298613669

    0.12773349470.12773349470.10211009070.1021100907

    0.09396051380.09396051380.14984958880.1498495888

    Low CBD:THC

    High CBD:THC

    Rating

    attentional bias

    Mean

    Descriptives

    IntoxicatedNot IntoxicatedStd. Error

    FoodDrugFoodDrug

    Low CBD:THC40.139652812529.0633804688-0.526738322683.012365580613.940997281418.643240227117.790069469710.9159953217

    High CBD:THC-9.080355875-45.773671843812.59588.178838633318.740275843815.475650047818.315051155410.5135063612

    Drug_intoxicated1

    2

    Drug Non_intoxicated1

    2

    Food Non-intoxicated1

    2

    attentional bias

    13.940997281418.7402758438

    18.643240227115.4756500478

    17.790069469718.3150511554

    10.915995321710.5135063612

    Low CBD:THC

    High CBD:THC

    Bias (ms)

  • 39

    Paranoia and ‘stoned’ effects

    • Levels of CBD in cannabis smoked did not impact on acute psychotic like effects of cannabis

    • No difference in ‘stoned’ ratings between high and low CBD groups

    Study 2: Naturalistic study of cannabinoids

    Morgan et al. (2011) Psychological Medicine

  • 40

    Acute effects of cannabinoids

    • Acutely CBD protects from memory impairment of THC

    • Greater attentional bias in people smoking low CBD cannabis

    Study 2: Naturalistic study – Chronic effects Study 2: Naturalistic study of cannabinoids

  • 41

    Chronic effects of cannabinoids on psychotic symptoms

    • Looked at CBD and THC in hair • Replicated previous findings Morgan & Curran (2008) • Psychotic symptoms higher in those smoking

    cannabis with no CBD – Highest in infrequent users smoking high THC

    cannabis with no CBD

    Study 2: Naturalistic study – Chronic effects Study 2: Naturalistic study of cannabinoids

  • 42

    Acute effects of cannabinoids in cannabis smokers: laboratory study

    PLACEBO 16mg CBD

    8mg THC 8mg THC +16 mg CBD

    • 48 participants • Selected to be:

    • 24 daily users • 24 less frequent

    • Of those • 50% High psychosis

    proneness / schizotypy : (top quartile)

    • 50% Low psychosis proneness / schizotypy (bottom quartile)

  • 43

    Acute effects of cannabinoids in cannabis smokers: laboratory study

    • Inhaled CBD and THC through a ‘Volcano’

    • Aimed to reverse the acute psychotic effects of THC in line with laboratory studies (Bhattarcharya et al., 2010)

  • 44

    • Psychotic symptoms greater following THC

    Study 3: Acute effects of CBD/THC in laboratory

  • 45

    CBD reduces THC induced psychotic symptoms?

    5

    10

    15

    20

    25

    30

    35

    40

    THC THC + CBD CBD Placebo

    PSI

    SC

    OR

    E

    Low schizotypy, recreational

    High schizotypy, recreational

    Low schizotypy, daily

    High schizotypy, daily

    Study 3: Acute effects of CBD/THC in laboratory

  • 46

    CBD and memory in the laboratory

  • 47

    CBD and memory

    • Measure startle response from electrical impulses in skin

  • 48

    CBD in the laboratory

  • 49

    CBD in the laboratory

    • CBD speeds up ‘forgetting’ of associations… ‘extinction learning’

    • Forgetting has important therapeutic implications in treatment of psychiatric disorders…

    • Phobias – e.g. spider with fear response • Substance use – e.g. drugs with pleasure

  • 50

    CBD to reduce cigarette smoking?

    • n=24 smokers not actively quitting

    • Half given CBD inhaler, half placebo

    • Ad hoc use over a week

    • 40% reduction in cigarette smoking in CBD group

    0

    20

    40

    60

    80

    100

    120

    Pre Post Follow-up

    Num

    ber

    of c

    igar

    ette

    s sm

    oked

    per

    w

    eek Placebo

    CBD

    **

    n

    Morgan et al., 2013 Addictive Behaviour

  • 51

    Use of CBD in therapy

  • 52

    How does cannabis act on the brain?

  • 53

    How does cannabis act on the brain?

    Raphael Mechoulam Asked Israeli police to give him 5kg cannabis. He discovered THC and later CBD.

    http://www.google.com/url?sa=i&rct=j&q=&esrc=s&frm=1&source=images&cd=&cad=rja&docid=426vnPZBmdEiYM&tbnid=QNJFlYs4jKID3M:&ved=0CAUQjRw&url=http://www.cannabisterapeutica.info/tag/farmaco/&ei=wVgHU_O4MYGw0QXk4IHgDw&bvm=bv.61725948,d.ZG4&psig=AFQjCNElvRF4iySoZt7j9NDfDK-IgOpxlw&ust=1393076656373952

  • 54

    How does cannabis act on the brain?

    Raphael Mechoulam Asked Israeli police to give him 5kg cannabis. He discovered THC and later CBD. Howlett, discovered cannabinoid receptors – CB1 in brain; CB2 immune system.

    http://www.google.com/url?sa=i&rct=j&q=&esrc=s&frm=1&source=images&cd=&cad=rja&docid=426vnPZBmdEiYM&tbnid=QNJFlYs4jKID3M:&ved=0CAUQjRw&url=http://www.cannabisterapeutica.info/tag/farmaco/&ei=wVgHU_O4MYGw0QXk4IHgDw&bvm=bv.61725948,d.ZG4&psig=AFQjCNElvRF4iySoZt7j9NDfDK-IgOpxlw&ust=1393076656373952

  • 55

    How does cannabis act on the brain?

    Raphael Mechoulam Asked Israeli police to give him 5kg cannabis. He discovered THC and later CBD. Howlett, discovered cannabinoid receptors – CB1 in brain; CB2 immune system.

    http://www.google.com/url?sa=i&rct=j&q=&esrc=s&frm=1&source=images&cd=&cad=rja&docid=426vnPZBmdEiYM&tbnid=QNJFlYs4jKID3M:&ved=0CAUQjRw&url=http://www.cannabisterapeutica.info/tag/farmaco/&ei=wVgHU_O4MYGw0QXk4IHgDw&bvm=bv.61725948,d.ZG4&psig=AFQjCNElvRF4iySoZt7j9NDfDK-IgOpxlw&ust=1393076656373952

  • 56

    How does cannabis act on the brain?

    Raphael Mechoulam Asked Israeli police to give him 5kg cannabis. He discovered THC and later CBD. Howlett, discovered cannabinoid receptors – CB1 in brain; CB2 immune system. Raphael’s team discovered the ‘brain’s own cannabis’ - anandamide (ananda = bliss/ delight in Sanscrit) & 2-AG. .

    http://www.google.com/url?sa=i&rct=j&q=&esrc=s&frm=1&source=images&cd=&cad=rja&docid=426vnPZBmdEiYM&tbnid=QNJFlYs4jKID3M:&ved=0CAUQjRw&url=http://www.cannabisterapeutica.info/tag/farmaco/&ei=wVgHU_O4MYGw0QXk4IHgDw&bvm=bv.61725948,d.ZG4&psig=AFQjCNElvRF4iySoZt7j9NDfDK-IgOpxlw&ust=1393076656373952

  • 57

    Endocannabinoids Phytocannabinoids Synthetic cannabinoids brain plant manufactured

    CB1 & CB2 receptors Pleasure, addiction, pain, appetite, memory,

    immune system, mental health

    http://www.easyvectors.com/assets/images/vectors/afbig/chemistry-lab-flask-clip-art.jpg

  • 58

    Endocannabinoids in psychosis • AEA increased in antipsychotic-

    naïve first-episode psychosis (Leweke et al., 1999, Guiffrida et al. 2004)

    • Drops off in chronic schiz • Modulate excessive DA release? • Downregulation of

    endocannabinoid signalling following repeated THC administration in rats (DiMarzo et al., 2000)

  • 59

    Looking at endocannabinoids in cannabis users

    • AEA in blood does not correlate with

    brain • Collected CSF from lumbar punctures • 21 cannabis users (mean age

    22.0±2.91) • 13 matched controls (mean age

    22.1±2.45 ) • PSI to assess psychotic symptoms

  • 60

    AEA in cannabis users

    0.05

    0.07

    0.09

    0.11

    0.13

    0.15

    0.17

    0.19

    Control Low Heavy

    AE

    A, p

    mol

    /mol

    Morgan et al., 2013 Brit J Psych

    r= -0.536, p=0.02

  • 61

    Endocannabinoids and psychosis

    • Lower AEA in heavy users • Chronic downregulation of anandamide through repeated

    THC administration • How cannabis increases risk of psychosis?

    • Negative correlation with symptom severity – Consistent with findings in psychosis

  • 62

    Endocannabinoids and Cannabinoids

    • CBD may block the reuptake and hydrolysis of anandamide

    • CBD increases levels of AEA in patients with schizophrenia

    • CBD improves psychotic symptoms in patients with schizophrenia (Leweke et al., 2012 Translational Psych)

  • 63

    Conclusions

    THC Induces anxiety Psychotic-like

    effects. Impairs

    memory and learning

    CBD Reduces anxiety Anti-psychotic

    effects Enhances learning

    and blocks THC memory loss

    http://www.texample.net/media/tikz/examples/PDF/yin-and-yang.pdf

  • 64

    Conclusions

    • CBD is emerging as an important medicine • CBD levels are declining in street cannabis

    – Alongside increasing levels of THC may increase the harms of the drug

    • Smoking hash / resin (if available) reduce the harm

  • 65

    What implications does our scientific understanding of cannabis have for

    debates about legalisation?

    • Taking control of the cannabis market could allow rich CBD forms of cannabis to become widely available.

    • This could help protect young people from the mental health harms of high THC/skunk forms.

  • 66

    Medical Marijuana: US

    www.leafly.com

    http://www.leafly.com

  • 67

    Medical Marijuana US

    www.leafly.com

    http://www.leafly.com

  • 68

    Medical Marijuana: US

    www.leafly.com

    http://www.leafly.com

  • 69

    Acknowledgements

    UCL Val Curran Tom Freeman Grainne Schafer Chelsea Gardner Emma Page Centre for Anaesthesia Brigitta Brandner Kate Chatten Sumit Galati Amod Manocha IoP John Powell CIMH Mannheim Markus Leweke Christina Schaefer

  • 70

    Thanks!

    Endocannabinoids, cannabinoids and cannabisCannabisCannabisCannabisCannabisCannabinoidsSlide Number 7Levels of THC and CBD in 3000 cannabis seizures UKIncreasing THC potency in UK cannabis seizuresCannabis samples collected, n=422CBD and THC levels CBD and THC levels Preferences for types of cannabis in 16-23 year oldsSlide Number 14Slide Number 15‘Skunk’ use linked to psychosisResearch questionResearch questionSlide Number 19Looking at cannabinoids in the hair…Looking at cannabinoids in the hair…Study 1: THC/CBD in hair Slide Number 23THC/CBD in hairTHC / CBDStudy 2: Naturalistic study of the effects of cannabinoids��Slide Number 27Slide Number 28Slide Number 29Slide Number 30Slide Number 31Slide Number 32Slide Number 33Slide Number 34Slide Number 35Slide Number 36Slide Number 37Slide Number 38Paranoia and ‘stoned’ effectsAcute effects of cannabinoidsChronic effects of cannabinoids on psychotic symptomsAcute effects of cannabinoids in cannabis smokers: laboratory studyAcute effects of cannabinoids in cannabis smokers: laboratory studySlide Number 44CBD reduces THC induced psychotic symptoms?CBD and memory in the laboratoryCBD and memoryCBD in the laboratoryCBD in the laboratoryCBD to reduce cigarette smoking?Use of CBD in therapy How does cannabis act on the brain?How does cannabis act on the brain?How does cannabis act on the brain?How does cannabis act on the brain?How does cannabis act on the brain?Slide Number 57Endocannabinoids in psychosisLooking at endocannabinoids in cannabis usersAEA in cannabis usersEndocannabinoids and psychosisEndocannabinoids and CannabinoidsConclusionsConclusions��What implications does our scientific understanding of cannabis have for debates about legalisation? �Medical Marijuana: USMedical Marijuana USMedical Marijuana: USSlide Number 69Slide Number 70