|
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result sql = JWH018, a common constituent of 'Spice' herbal blends, is a potent and efficacious cannabinoid CB receptor agonist.
JWH018, a common constituent of 'Spice' herbal blends, is a potent and efficacious cannabinoid CB receptor agonist.char = <;code = 60
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char = e;code = 101
char = r;code = 114
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = a;code = 97
char = l;code = 108
char = y;code = 121
char = s;code = 115
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = i;code = 105
char = t;code = 116
char = s;code = 115
char = ;code = 32
char = a;code = 97
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = E;code = 69
char = R;code = 82
char = K;code = 75
char = 1;code = 49
char = /;code = 47
char = 2;code = 50
char = ;code = 32
char = m;code = 109
char = i;code = 105
char = t;code = 116
char = o;code = 111
char = g;code = 103
char = e;code = 101
char = n;code = 110
char = ;code = 32
char = a;code = 97
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = t;code = 116
char = e;code = 101
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = k;code = 107
char = i;code = 105
char = n;code = 110
char = a;code = 97
char = s;code = 115
char = e;code = 101
char = ;code = 32
char = (;code = 40
char = M;code = 77
char = A;code = 65
char = P;code = 80
char = K;code = 75
char = );code = 41
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = t;code = 116
char = e;code = 101
char = r;code = 114
char = n;code = 110
char = a;code = 97
char = l;code = 108
char = i;code = 105
char = z;code = 122
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = C;code = 67
char = B;code = 66
char = (;code = 40
char = 1;code = 49
char = );code = 41
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = c;code = 99
char = e;code = 101
char = p;code = 112
char = t;code = 116
char = o;code = 111
char = r;code = 114
char = s;code = 115
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = H;code = 72
char = E;code = 69
char = K;code = 75
char = 2;code = 50
char = 9;code = 57
char = 3;code = 51
char = ;code = 32
char = c;code = 99
char = e;code = 101
char = l;code = 108
char = l;code = 108
char = s;code = 115
char = ;code = 32
char = s;code = 115
char = t;code = 116
char = a;code = 97
char = b;code = 98
char = l;code = 108
char = y;code = 121
char = ;code = 32
char = e;code = 101
char = x;code = 120
char = p;code = 112
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = s;code = 115
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = i;code = 105
char = s;code = 115
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = c;code = 99
char = e;code = 101
char = p;code = 112
char = t;code = 116
char = o;code = 111
char = r;code = 114
char = .;code = 46
char = <;code = 60
char = b;code = 98
char = r;code = 114
char = /;code = 47
char = >;code = 62
char = <;code = 60
char = b;code = 98
char = r;code = 114
char = /;code = 47
char = >;code = 62
char = <;code = 60
char = b;code = 98
char = >;code = 62
char = K;code = 75
char = E;code = 69
char = Y;code = 89
char = ;code = 32
char = R;code = 82
char = E;code = 69
char = S;code = 83
char = U;code = 85
char = L;code = 76
char = T;code = 84
char = S;code = 83
char = ;code = 32
char = :;code = 58
char = ;code = 32
char = <;code = 60
char = /;code = 47
char = b;code = 98
char = >;code = 62
char = I;code = 73
char = n;code = 110
char = ;code = 32
char = c;code = 99
char = u;code = 117
char = l;code = 108
char = t;code = 116
char = u;code = 117
char = r;code = 114
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = a;code = 97
char = u;code = 117
char = t;code = 116
char = a;code = 97
char = p;code = 112
char = t;code = 116
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = h;code = 104
char = i;code = 105
char = p;code = 112
char = p;code = 112
char = o;code = 111
char = c;code = 99
char = a;code = 97
char = m;code = 109
char = p;code = 112
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = n;code = 110
char = e;code = 101
char = u;code = 117
char = r;code = 114
char = o;code = 111
char = n;code = 110
char = s;code = 115
char = ,;code = 44
char = ;code = 32
char = J;code = 74
char = W;code = 87
char = H;code = 72
char = 0;code = 48
char = 1;code = 49
char = 8;code = 56
char = ;code = 32
char = p;code = 112
char = o;code = 111
char = t;code = 116
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = l;code = 108
char = y;code = 121
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = h;code = 104
char = i;code = 105
char = b;code = 98
char = i;code = 105
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = e;code = 101
char = x;code = 120
char = c;code = 99
char = i;code = 105
char = t;code = 116
char = a;code = 97
char = t;code = 116
char = o;code = 111
char = r;code = 114
char = y;code = 121
char = ;code = 32
char = p;code = 112
char = o;code = 111
char = s;code = 115
char = t;code = 116
char = s;code = 115
char = y;code = 121
char = n;code = 110
char = a;code = 97
char = p;code = 112
char = t;code = 116
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = c;code = 99
char = u;code = 117
char = r;code = 114
char = r;code = 114
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = s;code = 115
char = ;code = 32
char = (;code = 40
char = I;code = 73
char = C;code = 67
char = (;code = 40
char = 5;code = 53
char = 0;code = 48
char = );code = 41
char = =;code = 61
char = ;code = 32
char = 1;code = 49
char = 4;code = 52
char = .;code = 46
char = 9;code = 57
char = ;code = 32
char = n;code = 110
char = M;code = 77
char = );code = 41
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = n;code = 110
char = c;code = 99
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = r;code = 114
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = -;code = 45
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = C;code = 67
char = B;code = 66
char = (;code = 40
char = 1;code = 49
char = );code = 41
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = c;code = 99
char = e;code = 101
char = p;code = 112
char = t;code = 116
char = o;code = 111
char = r;code = 114
char = -;code = 45
char = d;code = 100
char = e;code = 101
char = p;code = 112
char = e;code = 101
char = n;code = 110
char = d;code = 100
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = ;code = 32
char = m;code = 109
char = a;code = 97
char = n;code = 110
char = n;code = 110
char = e;code = 101
char = r;code = 114
char = .;code = 46
char = ;code = 32
char = F;code = 70
char = u;code = 117
char = r;code = 114
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = r;code = 114
char = m;code = 109
char = o;code = 111
char = r;code = 114
char = e;code = 101
char = ,;code = 44
char = ;code = 32
char = i;code = 105
char = t;code = 116
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = c;code = 99
char = r;code = 114
char = e;code = 101
char = a;code = 97
char = s;code = 115
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = E;code = 69
char = R;code = 82
char = K;code = 75
char = 1;code = 49
char = /;code = 47
char = 2;code = 50
char = ;code = 32
char = M;code = 77
char = A;code = 65
char = P;code = 80
char = K;code = 75
char = ;code = 32
char = p;code = 112
char = h;code = 104
char = o;code = 111
char = s;code = 115
char = p;code = 112
char = h;code = 104
char = o;code = 111
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char = y;code = 121
char = l;code = 108
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = (;code = 40
char = E;code = 69
char = C;code = 67
char = (;code = 40
char = 5;code = 53
char = 0;code = 48
char = );code = 41
char = =;code = 61
char = ;code = 32
char = 4;code = 52
char = .;code = 46
char = 4;code = 52
char = ;code = 32
char = n;code = 110
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char = );code = 41
char = .;code = 46
char = ;code = 32
char = W;code = 87
char = e;code = 101
char = ;code = 32
char = a;code = 97
char = l;code = 108
char = s;code = 115
char = o;code = 111
char = ;code = 32
char = f;code = 102
char = o;code = 111
char = u;code = 117
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = a;code = 97
char = t;code = 116
char = ;code = 32
char = J;code = 74
char = W;code = 87
char = H;code = 72
char = 0;code = 48
char = 1;code = 49
char = 8;code = 56
char = ;code = 32
char = p;code = 112
char = o;code = 111
char = t;code = 116
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = l;code = 108
char = y;code = 121
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char = i;code = 105
char = n;code = 110
char = d;code = 100
char = u;code = 117
char = c;code = 99
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = r;code = 114
char = a;code = 97
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char = i;code = 105
char = d;code = 100
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char = a;code = 97
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char = d;code = 100
char = ;code = 32
char = r;code = 114
char = o;code = 111
char = b;code = 98
char = u;code = 117
char = s;code = 115
char = t;code = 116
char = ;code = 32
char = C;code = 67
char = B;code = 66
char = (;code = 40
char = 1;code = 49
char = );code = 41
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = c;code = 99
char = e;code = 101
char = p;code = 112
char = t;code = 116
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = t;code = 116
char = e;code = 101
char = r;code = 114
char = n;code = 110
char = a;code = 97
char = l;code = 108
char = i;code = 105
char = z;code = 122
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = (;code = 40
char = E;code = 69
char = C;code = 67
char = (;code = 40
char = 5;code = 53
char = 0;code = 48
char = );code = 41
char = =;code = 61
char = ;code = 32
char = 2;code = 50
char = .;code = 46
char = 8;code = 56
char = ;code = 32
char = n;code = 110
char = M;code = 77
char = ;;code = 59
char = ;code = 32
char = t;code = 116
char = (;code = 40
char = 1;code = 49
char = /;code = 47
char = 2;code = 50
char = );code = 41
char = =;code = 61
char = ;code = 32
char = 1;code = 49
char = 7;code = 55
char = .;code = 46
char = 3;code = 51
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char = m;code = 109
char = i;code = 105
char = n;code = 110
char = );code = 41
char = .;code = 46
char = <;code = 60
char = b;code = 98
char = r;code = 114
char = /;code = 47
char = >;code = 62
char = <;code = 60
char = b;code = 98
char = r;code = 114
char = /;code = 47
char = >;code = 62
char = <;code = 60
char = b;code = 98
char = >;code = 62
char = C;code = 67
char = O;code = 79
char = N;code = 78
char = C;code = 67
char = L;code = 76
char = U;code = 85
char = S;code = 83
char = I;code = 73
char = O;code = 79
char = N;code = 78
char = S;code = 83
char = ;code = 32
char = A;code = 65
char = N;code = 78
char = D;code = 68
char = ;code = 32
char = I;code = 73
char = M;code = 77
char = P;code = 80
char = L;code = 76
char = I;code = 73
char = C;code = 67
char = A;code = 65
char = T;code = 84
char = I;code = 73
char = O;code = 79
char = N;code = 78
char = S;code = 83
char = ;code = 32
char = :;code = 58
char = ;code = 32
char = <;code = 60
char = /;code = 47
char = b;code = 98
char = >;code = 62
char = J;code = 74
char = W;code = 87
char = H;code = 72
char = 0;code = 48
char = 1;code = 49
char = 8;code = 56
char = ,;code = 44
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = m;code = 109
char = i;code = 105
char = n;code = 110
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = ;code = 32
char = c;code = 99
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char = m;code = 109
char = p;code = 112
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char = n;code = 110
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = s;code = 115
char = e;code = 101
char = v;code = 118
char = e;code = 101
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char = a;code = 97
char = l;code = 108
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char = h;code = 104
char = e;code = 101
char = r;code = 114
char = b;code = 98
char = a;code = 97
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char = ;code = 32
char = p;code = 112
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char = e;code = 101
char = p;code = 112
char = a;code = 97
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char = a;code = 97
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char = i;code = 105
char = o;code = 111
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char = s;code = 115
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char = k;code = 107
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char = e;code = 101
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char = a;code = 97
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char = e;code = 101
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char = f;code = 102
char = e;code = 101
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char = t;code = 116
char = i;code = 105
char = v;code = 118
char = e;code = 101
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char = C;code = 67
char = B;code = 66
char = (;code = 40
char = 1;code = 49
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char = c;code = 99
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char = o;code = 111
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char = a;code = 97
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char = i;code = 105
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char = a;code = 97
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char = a;code = 97
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char = e;code = 101
char = s;code = 115
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char = m;code = 109
char = u;code = 117
char = l;code = 108
char = t;code = 116
char = i;code = 105
char = p;code = 112
char = l;code = 108
char = e;code = 101
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char = C;code = 67
char = B;code = 66
char = (;code = 40
char = 1;code = 49
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char = r;code = 114
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char = c;code = 99
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char = p;code = 112
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char = o;code = 111
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char = s;code = 115
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char = a;code = 97
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char = a;code = 97
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char = h;code = 104
char = w;code = 119
char = a;code = 97
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char = ;code = 32
char = T;code = 84
char = h;code = 104
char = u;code = 117
char = s;code = 115
char = ,;code = 44
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char = i;code = 105
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char = k;code = 107
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char = a;code = 97
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char = t;code = 116
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char = b;code = 98
char = j;code = 106
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char = c;code = 99
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char = v;code = 118
char = e;code = 101
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char = e;code = 101
char = f;code = 102
char = f;code = 102
char = e;code = 101
char = c;code = 99
char = t;code = 116
char = s;code = 115
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char = o;code = 111
char = f;code = 102
char = ;code = 32
char = ';code = 39
char = S;code = 83
char = p;code = 112
char = i;code = 105
char = c;code = 99
char = e;code = 101
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char = a;code = 97
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char = e;code = 101
char = ;code = 32
char = d;code = 100
char = u;code = 117
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char = t;code = 116
char = o;code = 111
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char = a;code = 97
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char = i;code = 105
char = v;code = 118
char = a;code = 97
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char = o;code = 111
char = n;code = 110
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char = o;code = 111
char = f;code = 102
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char = b;code = 98
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char = n;code = 110
char = o;code = 111
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char = d;code = 100
char = ;code = 32
char = C;code = 67
char = B;code = 66
char = (;code = 40
char = 1;code = 49
char = );code = 41
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result sql = BACKGROUND AND PURPOSE : 'Spice' is an herbal blend primarily marketed in Europe as a mild hallucinogen with prominent cannabis-like effects and as a legal alternative to cannabis. However, a recent report identified a number of synthetic additives in samples of 'Spice'. One of these, the indole derivative JWH018, is a ligand for the cannabinoid receptor 1 (CB(1)) cannabinoid receptor and inhibits cAMP production in CB(1) receptor-expressing CHO cells. Other effects of JWH018 on CB(1) receptor-mediated signalling are not known, particularly in neurons. Here we have evaluated the signalling pathways activated by JWH018 at CB(1) receptors.
EXPERIMENTAL APPROACH : We investigated the effects of JWH018 on neurotransmission in cultured autaptic hippocampal neurons. We further analysed its activation of ERK1/2 mitogen activated protein kinase (MAPK) and internalization of CB(1) receptors in HEK293 cells stably expressing this receptor.
KEY RESULTS : In cultured autaptic hippocampal neurons, JWH018 potently inhibited excitatory postsynaptic currents (IC(50)= 14.9 nM) in a concentration- and CB(1) receptor-dependent manner. Furthermore, it increased ERK1/2 MAPK phosphorylation (EC(50)= 4.4 nM). We also found that JWH018 potently induced rapid and robust CB(1) receptor internalization (EC(50)= 2.8 nM; t(1/2)= 17.3 min).
CONCLUSIONS AND IMPLICATIONS : JWH018, a prominent component of several herbal preparations marketed for their psychoactivity, is a potent and effective CB(1) receptor agonist that activates multiple CB(1) receptor signalling pathways. Thus, it is likely that the subjective effects of 'Spice' are due to activation of cannabinoid CB(1) receptors by JWH018, added to this herbal preparation.
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result sql = JWH018, a common constituent of 'Spice' herbal blends, is a potent and efficacious cannabinoid CB receptor agonist.
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char = e;code = 101
char = f;code = 102
char = f;code = 102
char = e;code = 101
char = c;code = 99
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char = o;code = 111
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char = ;code = 32
char = J;code = 74
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char = H;code = 72
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char = n;code = 110
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char = t;code = 116
char = r;code = 114
char = a;code = 97
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char = m;code = 109
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char = s;code = 115
char = s;code = 115
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char = o;code = 111
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char = i;code = 105
char = n;code = 110
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char = c;code = 99
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char = l;code = 108
char = t;code = 116
char = u;code = 117
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char = t;code = 116
char = a;code = 97
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char = i;code = 105
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char = p;code = 112
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char = a;code = 97
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char = n;code = 110
char = e;code = 101
char = u;code = 117
char = r;code = 114
char = o;code = 111
char = n;code = 110
char = s;code = 115
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char = ;code = 32
char = W;code = 87
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char = f;code = 102
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char = t;code = 116
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char = r;code = 114
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char = a;code = 97
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char = a;code = 97
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char = y;code = 121
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char = s;code = 115
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char = a;code = 97
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char = v;code = 118
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
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char = o;code = 111
char = f;code = 102
char = ;code = 32
char = E;code = 69
char = R;code = 82
char = K;code = 75
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char = 2;code = 50
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char = a;code = 97
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char = a;code = 97
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char = d;code = 100
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char = r;code = 114
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char = t;code = 116
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char = i;code = 105
char = n;code = 110
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char = k;code = 107
char = i;code = 105
char = n;code = 110
char = a;code = 97
char = s;code = 115
char = e;code = 101
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char = (;code = 40
char = M;code = 77
char = A;code = 65
char = P;code = 80
char = K;code = 75
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char = ;code = 32
char = a;code = 97
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char = d;code = 100
char = ;code = 32
char = i;code = 105
char = n;code = 110
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char = e;code = 101
char = r;code = 114
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char = a;code = 97
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char = i;code = 105
char = z;code = 122
char = a;code = 97
char = t;code = 116
char = i;code = 105
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char = n;code = 110
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char = o;code = 111
char = f;code = 102
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char = C;code = 67
char = B;code = 66
char = (;code = 40
char = 1;code = 49
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char = ;code = 32
char = r;code = 114
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char = c;code = 99
char = e;code = 101
char = p;code = 112
char = t;code = 116
char = o;code = 111
char = r;code = 114
char = s;code = 115
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = H;code = 72
char = E;code = 69
char = K;code = 75
char = 2;code = 50
char = 9;code = 57
char = 3;code = 51
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char = c;code = 99
char = e;code = 101
char = l;code = 108
char = l;code = 108
char = s;code = 115
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char = s;code = 115
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char = a;code = 97
char = b;code = 98
char = l;code = 108
char = y;code = 121
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char = e;code = 101
char = x;code = 120
char = p;code = 112
char = r;code = 114
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char = s;code = 115
char = s;code = 115
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = t;code = 116
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char = i;code = 105
char = s;code = 115
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char = r;code = 114
char = e;code = 101
char = c;code = 99
char = e;code = 101
char = p;code = 112
char = t;code = 116
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char = <;code = 60
char = b;code = 98
char = r;code = 114
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char = >;code = 62
char = <;code = 60
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char = r;code = 114
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char = >;code = 62
char = <;code = 60
char = b;code = 98
char = >;code = 62
char = K;code = 75
char = E;code = 69
char = Y;code = 89
char = ;code = 32
char = R;code = 82
char = E;code = 69
char = S;code = 83
char = U;code = 85
char = L;code = 76
char = T;code = 84
char = S;code = 83
char = ;code = 32
char = :;code = 58
char = ;code = 32
char = <;code = 60
char = /;code = 47
char = b;code = 98
char = >;code = 62
char = I;code = 73
char = n;code = 110
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char = c;code = 99
char = u;code = 117
char = l;code = 108
char = t;code = 116
char = u;code = 117
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char = d;code = 100
char = ;code = 32
char = a;code = 97
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char = t;code = 116
char = a;code = 97
char = p;code = 112
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char = i;code = 105
char = c;code = 99
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char = h;code = 104
char = i;code = 105
char = p;code = 112
char = p;code = 112
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char = m;code = 109
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char = a;code = 97
char = l;code = 108
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char = u;code = 117
char = r;code = 114
char = o;code = 111
char = n;code = 110
char = s;code = 115
char = ,;code = 44
char = ;code = 32
char = J;code = 74
char = W;code = 87
char = H;code = 72
char = 0;code = 48
char = 1;code = 49
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char = p;code = 112
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char = t;code = 116
char = l;code = 108
char = y;code = 121
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char = i;code = 105
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char = h;code = 104
char = i;code = 105
char = b;code = 98
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char = t;code = 116
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char = c;code = 99
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char = t;code = 116
char = a;code = 97
char = t;code = 116
char = o;code = 111
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char = y;code = 121
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char = p;code = 112
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char = s;code = 115
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char = a;code = 97
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char = i;code = 105
char = c;code = 99
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char = c;code = 99
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char = r;code = 114
char = e;code = 101
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char = s;code = 115
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char = I;code = 73
char = C;code = 67
char = (;code = 40
char = 5;code = 53
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char = ;code = 32
char = 1;code = 49
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char = B;code = 66
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char = ;code = 32
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char = c;code = 99
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char = m;code = 109
char = a;code = 97
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char = n;code = 110
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char = .;code = 46
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char = F;code = 70
char = u;code = 117
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char = e;code = 101
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char = i;code = 105
char = t;code = 116
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char = i;code = 105
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char = e;code = 101
char = a;code = 97
char = s;code = 115
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char = d;code = 100
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char = E;code = 69
char = R;code = 82
char = K;code = 75
char = 1;code = 49
char = /;code = 47
char = 2;code = 50
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char = M;code = 77
char = A;code = 65
char = P;code = 80
char = K;code = 75
char = ;code = 32
char = p;code = 112
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char = o;code = 111
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char = a;code = 97
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char = i;code = 105
char = o;code = 111
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char = ;code = 32
char = (;code = 40
char = E;code = 69
char = C;code = 67
char = (;code = 40
char = 5;code = 53
char = 0;code = 48
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char = =;code = 61
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char = 4;code = 52
char = .;code = 46
char = 4;code = 52
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char = n;code = 110
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char = .;code = 46
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char = W;code = 87
char = e;code = 101
char = ;code = 32
char = a;code = 97
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char = s;code = 115
char = o;code = 111
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char = f;code = 102
char = o;code = 111
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char = d;code = 100
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char = t;code = 116
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char = a;code = 97
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char = J;code = 74
char = W;code = 87
char = H;code = 72
char = 0;code = 48
char = 1;code = 49
char = 8;code = 56
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char = i;code = 105
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char = u;code = 117
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char = e;code = 101
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char = r;code = 114
char = o;code = 111
char = b;code = 98
char = u;code = 117
char = s;code = 115
char = t;code = 116
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char = C;code = 67
char = B;code = 66
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char = 1;code = 49
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char = a;code = 97
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char = z;code = 122
char = a;code = 97
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char = i;code = 105
char = o;code = 111
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char = E;code = 69
char = C;code = 67
char = (;code = 40
char = 5;code = 53
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char = );code = 41
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char = ;code = 32
char = 2;code = 50
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char = 8;code = 56
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char = n;code = 110
char = M;code = 77
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char = ;code = 32
char = t;code = 116
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char = 1;code = 49
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char = =;code = 61
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char = 1;code = 49
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char = <;code = 60
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char = /;code = 47
char = >;code = 62
char = <;code = 60
char = b;code = 98
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char = C;code = 67
char = O;code = 79
char = N;code = 78
char = C;code = 67
char = L;code = 76
char = U;code = 85
char = S;code = 83
char = I;code = 73
char = O;code = 79
char = N;code = 78
char = S;code = 83
char = ;code = 32
char = A;code = 65
char = N;code = 78
char = D;code = 68
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char = L;code = 76
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char = C;code = 67
char = A;code = 65
char = T;code = 84
char = I;code = 73
char = O;code = 79
char = N;code = 78
char = S;code = 83
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char = :;code = 58
char = ;code = 32
char = <;code = 60
char = /;code = 47
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char = J;code = 74
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char = H;code = 72
char = 0;code = 48
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char = a;code = 97
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char = k;code = 107
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char = t;code = 116
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char = C;code = 67
char = B;code = 66
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char = 1;code = 49
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char = u;code = 117
char = l;code = 108
char = t;code = 116
char = i;code = 105
char = p;code = 112
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char = C;code = 67
char = B;code = 66
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char = w;code = 119
char = a;code = 97
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char = T;code = 84
char = h;code = 104
char = u;code = 117
char = s;code = 115
char = ,;code = 44
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result sql = BACKGROUND AND PURPOSE : 'Spice' is an herbal blend primarily marketed in Europe as a mild hallucinogen with prominent cannabis-like effects and as a legal alternative to cannabis. However, a recent report identified a number of synthetic additives in samples of 'Spice'. One of these, the indole derivative JWH018, is a ligand for the cannabinoid receptor 1 (CB(1)) cannabinoid receptor and inhibits cAMP production in CB(1) receptor-expressing CHO cells. Other effects of JWH018 on CB(1) receptor-mediated signalling are not known, particularly in neurons. Here we have evaluated the signalling pathways activated by JWH018 at CB(1) receptors.
EXPERIMENTAL APPROACH : We investigated the effects of JWH018 on neurotransmission in cultured autaptic hippocampal neurons. We further analysed its activation of ERK1/2 mitogen activated protein kinase (MAPK) and internalization of CB(1) receptors in HEK293 cells stably expressing this receptor.
KEY RESULTS : In cultured autaptic hippocampal neurons, JWH018 potently inhibited excitatory postsynaptic currents (IC(50)= 14.9 nM) in a concentration- and CB(1) receptor-dependent manner. Furthermore, it increased ERK1/2 MAPK phosphorylation (EC(50)= 4.4 nM). We also found that JWH018 potently induced rapid and robust CB(1) receptor internalization (EC(50)= 2.8 nM; t(1/2)= 17.3 min).
CONCLUSIONS AND IMPLICATIONS : JWH018, a prominent component of several herbal preparations marketed for their psychoactivity, is a potent and effective CB(1) receptor agonist that activates multiple CB(1) receptor signalling pathways. Thus, it is likely that the subjective effects of 'Spice' are due to activation of cannabinoid CB(1) receptors by JWH018, added to this herbal preparation.
Publication: Br. J. Pharmacol. 2010 Jun ;160(3)::585-93. :doi: 10.1111/j.1476-5381.2009.00582.x.
Publication Date: 2010 Jun
Study Author(s): Atwood, Brady K;Huffman, John;Straiker, Alex;Mackie, Ken;
Institution: The Gill Center and the Department of Psychological & Brain Sciences, Indiana University, Bloomington, IN 47405, USA.
Shortcut link to this study:
Publication Date: 2010 Jun
Study Author(s): Atwood, Brady K;Huffman, John;Straiker, Alex;Mackie, Ken;
Institution: The Gill Center and the Department of Psychological & Brain Sciences, Indiana University, Bloomington, IN 47405, USA.
Shortcut link to this study:
BACKGROUND AND PURPOSE : 'Spice' is an herbal blend primarily marketed in Europe as a mild hallucinogen with prominent cannabis-like effects and as a legal alternative to cannabis. However, a recent report identified a number of synthetic additives in samples of 'Spice'. One of these, the indole derivative JWH018, is a ligand for the cannabinoid receptor 1 (CB(1)) cannabinoid receptor and inhibits cAMP production in CB(1) receptor-expressing CHO cells. Other effects of JWH018 on CB(1) receptor-mediated signalling are not known, particularly in neurons. Here we have evaluated the signalling pathways activated by JWH018 at CB(1) receptors.
EXPERIMENTAL APPROACH : We investigated the effects of JWH018 on neurotransmission in cultured autaptic hippocampal neurons. We further analysed its activation of ERK1/2 mitogen activated protein kinase (MAPK) and internalization of CB(1) receptors in HEK293 cells stably expressing this receptor.
KEY RESULTS : In cultured autaptic hippocampal neurons, JWH018 potently inhibited excitatory postsynaptic currents (IC(50)= 14.9 nM) in a concentration- and CB(1) receptor-dependent manner. Furthermore, it increased ERK1/2 MAPK phosphorylation (EC(50)= 4.4 nM). We also found that JWH018 potently induced rapid and robust CB(1) receptor internalization (EC(50)= 2.8 nM; t(1/2)= 17.3 min).
CONCLUSIONS AND IMPLICATIONS : JWH018, a prominent component of several herbal preparations marketed for their psychoactivity, is a potent and effective CB(1) receptor agonist that activates multiple CB(1) receptor signalling pathways. Thus, it is likely that the subjective effects of 'Spice' are due to activation of cannabinoid CB(1) receptors by JWH018, added to this herbal preparation.
EXPERIMENTAL APPROACH : We investigated the effects of JWH018 on neurotransmission in cultured autaptic hippocampal neurons. We further analysed its activation of ERK1/2 mitogen activated protein kinase (MAPK) and internalization of CB(1) receptors in HEK293 cells stably expressing this receptor.
KEY RESULTS : In cultured autaptic hippocampal neurons, JWH018 potently inhibited excitatory postsynaptic currents (IC(50)= 14.9 nM) in a concentration- and CB(1) receptor-dependent manner. Furthermore, it increased ERK1/2 MAPK phosphorylation (EC(50)= 4.4 nM). We also found that JWH018 potently induced rapid and robust CB(1) receptor internalization (EC(50)= 2.8 nM; t(1/2)= 17.3 min).
CONCLUSIONS AND IMPLICATIONS : JWH018, a prominent component of several herbal preparations marketed for their psychoactivity, is a potent and effective CB(1) receptor agonist that activates multiple CB(1) receptor signalling pathways. Thus, it is likely that the subjective effects of 'Spice' are due to activation of cannabinoid CB(1) receptors by JWH018, added to this herbal preparation.
PMID: 20100276
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